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    Abnormal premolar eruption: classification, aetiology, and treatment based on a case series study. Kjær I European archives of paediatric dentistry : official journal of the European Academy of Paediatric Dentistry AIM:The aim of this case series study is to classify deviations in mandibular and maxillary premolar eruption according to aetiology, with a focus on the resorption pattern in the preceding primary molars. The purpose is also to give treatment guidance based on aetiology. MATERIALS AND METHODS:Radiographic material from 64 cases with abnormal premolar eruptions were grouped into three eruptions phases: Phase 1, from tooth bud to early root formation, sub-grouped according to "ankylosis" or "not ankylosis" of the primary molars; Phase 2, from start of eruption to the penetration of gingiva, sub-grouped according to normal or abnormal resorption of the primary molars and Phase 3, eruption after penetration of gingiva. RESULTS:Phase 1: early ankylosis of primary molars, ectopic locations of the premolar crown, including occlusally displacement in relation to the primary molar, are demonstrated. Not ankylosed primary molar: different positions, even an upside-down position of the premolar, are demonstrated. The conditions are explained in relation to the early migration pattern of the premolar tooth bud. Regarding treatment, in cases with ankylosed primary molars these should be extracted as soon as diagnosed and in cases with not ankylosed primary molars these should be extracted when root formation of the premolars has started. The premolars should be observed and saved if possible. Phase 2: non-exfoliation of primary molar, aetiology and treatment of premolars depend on tissue types involved. In bone dysplasia, the eruption of premolars is delayed. In these cases, the primary molars should be extracted when eruptive movements of the premolars have started. In cases with ectoderm deviation, the crown follicle does not function normally during the resorption of the primary molars and the recommended treatment is extraction of primary molars before root closure of premolars. In cases in Phase 2 where the premolars were ankylosed these should be surgical removed. Phase 3: different aetiologies are highlighted, with focus on abnormal innervation and enzyme defects. The premolars are seemingly ankylosed, and surgery might be the only treatment. CONCLUSION:The case series presented demonstrate how ectopic and arrested premolars have different aetiologies and as a consequence, different treatments. The study highlights several aspects in pathological eruption, which still need to be elucidated. 10.1007/s40368-021-00658-7
    Activins in reproductive biology and beyond. Wijayarathna R,de Kretser D M Human reproduction update BACKGROUND:Activins are members of the pleiotrophic family of the transforming growth factor-beta (TGF-β) superfamily of cytokines, initially isolated for their capacity to induce the release of FSH from pituitary extracts. Subsequent research has demonstrated that activins are involved in multiple biological functions including the control of inflammation, fibrosis, developmental biology and tumourigenesis. This review summarizes the current knowledge on the roles of activin in reproductive and developmental biology. It also discusses interesting advances in the field of modulating the bioactivity of activins as a therapeutic target, which would undoubtedly be beneficial for patients with reproductive pathology. METHODS:A comprehensive literature search was carried out using PUBMED and Google Scholar databases to identify studies in the English language which have contributed to the advancement of the field of activin biology, since its initial isolation in 1987 until July 2015. 'Activin', 'testis', 'ovary', 'embryonic development' and 'therapeutic targets' were used as the keywords in combination with other search phrases relevant to the topic of activin biology. RESULTS:Activins, which are dimers of inhibin β subunits, act via a classical TGF-β signalling pathway. The bioactivity of activin is regulated by two endogenous inhibitors, inhibin and follistatin. Activin is a major regulator of testicular and ovarian development. In the ovary, activin A promotes oocyte maturation and regulates granulosa cell steroidogenesis. It is also essential in endometrial repair following menstruation, decidualization and maintaining pregnancy. Dysregulation of the activin-follistatin-inhibin system leads to disorders of female reproduction and pregnancy, including polycystic ovary syndrome, ectopic pregnancy, miscarriage, fetal growth restriction, gestational diabetes, pre-eclampsia and pre-term birth. Moreover, a rise in serum activin A, accompanied by elevated FSH, is characteristic of female reproductive aging. In the male, activin A is an autocrine and paracrine modulator of germ cell development and Sertoli cell proliferation. Disruption of normal activin signalling is characteristic of many tumours affecting reproductive organs, including endometrial carcinoma, cervical cancer, testicular and ovarian cancer as well as prostate cancer. While activin A and B aid the progression of many tumours of the reproductive organs, activin C acts as a tumour suppressor. Activins are important in embryonic induction, morphogenesis of branched glandular organs, development of limbs and nervous system, craniofacial and dental development and morphogenesis of the Wolffian duct. CONCLUSIONS:The field of activin biology has advanced considerably since its initial discovery as an FSH stimulating agent. Now, activin is well known as a growth factor and cytokine that regulates many aspects of reproductive biology, developmental biology and also inflammation and immunological mechanisms. Current research provides evidence for novel roles of activins in maintaining the structure and function of reproductive and other organ systems. The fact that activin A is elevated both locally as well as systemically in major disorders of the reproductive system makes it an important biomarker. Given the established role of activin A as a pro-inflammatory and pro-fibrotic agent, studies of its involvement in disorders of reproduction resulting from these processes should be examined. Follistatin, as a key regulator of the biological actions of activin, should be evaluated as a therapeutic agent in conditions where activin A overexpression is established as a contributing factor. 10.1093/humupd/dmv058
    Leptin Induces Odontogenic Differentiation and Angiogenesis in Human Dental Pulp Cells via Activation of the Mitogen-activated Protein Kinase Signaling Pathway. Ngo Viet Anh,Jung Ji-Yeon,Koh Jeong-Tae,Oh Won-Mann,Hwang Yun-Chan,Lee Bin-Na Journal of endodontics INTRODUCTION:Up-regulation of odontogenic differentiation, dentin formation, and angiogenesis in dental pulp are key factors in vital pulp therapy. The aim of this study was to investigate whether leptin could promote odontogenic differentiation and angiogenesis in human dental pulp cells (hDPCs). In addition, the involvement of the intracellular signaling pathway in these effects was determined. METHODS:The viability of hDPCs treated with leptin was examined using the water soluble tetrazolium salt-1 assay. Real-time polymerase chain reaction was performed to determine messenger RNA (mRNA) expression levels of odontogenic and angiogenic markers. Western blot analysis was used to measure odontogenic and angiogenic protein expression levels and assess mitogen-activated protein kinase (MAPK) pathway involvement. Alkaline phosphatase (ALP) and alizarin red staining were used to evaluate expression levels of ALP and calcified nodule formation after treatment with leptin and/or the presence of MAPK inhibitors. RESULTS:All concentrations of leptin used in this study did not significantly affect the viability of hDPCs. However, mRNA and protein levels of odontogenic and angiogenic markers, ALP activity, and calcified nodule formation were significantly increased in the leptin-treated group compared with those in the control group. Leptin enhanced phosphorylation of extracellular signal-related kinases, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinases within 5 minutes after treatment. However, leptin-induced dentin sialophosphoprotein and vascular endothelial growth factor protein expression and mineralization were appreciably blocked by the presence of MAPK inhibitors. CONCLUSIONS:Leptin can induce angiogenesis, odontogenic differentiation, and mineralization in hDPCs via activating the MAPK signaling pathway. 10.1016/j.joen.2017.11.018
    Hsa-let-7c controls the committed differentiation of IGF-1-treated mesenchymal stem cells derived from dental pulps by targeting IGF-1R via the MAPK pathways. Liu Gen-Xia,Ma Shu,Li Yao,Yu Yan,Zhou Yi-Xiang,Lu Ya-Die,Jin Lin,Wang Zi-Lu,Yu Jin-Hua Experimental & molecular medicine The putative tumor suppressor microRNA let-7c is extensively associated with the biological properties of cancer cells. However, the potential involvement of let-7c in the differentiation of mesenchymal stem cells has not been fully explored. In this study, we investigated the influence of hsa-let-7c (let-7c) on the proliferation and differentiation of human dental pulp-derived mesenchymal stem cells (DPMSCs) treated with insulin-like growth factor 1 (IGF-1) via flow cytometry, CCK-8 assays, alizarin red staining, real-time RT-PCR, and western blotting. In general, the proliferative capabilities and cell viability of DPMSCs were not significantly affected by the overexpression or deletion of let-7c. However, overexpression of let-7c significantly inhibited the expression of IGF-1 receptor (IGF-1R) and downregulated the osteo/odontogenic differentiation of DPMSCs, as indicated by decreased levels of several osteo/odontogenic markers (osteocalcin, osterix, runt-related transcription factor 2, dentin sialophosphoprotein, dentin sialoprotein, alkaline phosphatase, type 1 collagen, and dentin matrix protein 1) in IGF-1-treated DPMSCs. Inversely, deletion of let-7c resulted in increased IGF-1R levels and enhanced osteo/odontogenic differentiation. Furthermore, the ERK, JNK, and P38 MAPK pathways were significantly inhibited following the overexpression of let-7c in DPMSCs. Deletion of let-7c promoted the activation of the JNK and P38 MAPK pathways. Our cumulative findings indicate that Let-7c can inhibit the osteo/odontogenic differentiation of IGF-1-treated DPMSCs by targeting IGF-1R via the JNK/P38 MAPK signaling pathways. 10.1038/s12276-018-0048-7
    Insulin-like growth factor 1 promotes the proliferation and committed differentiation of human dental pulp stem cells through MAPK pathways. Lv Taohong,Wu Yongzheng,Mu Chao,Liu Genxia,Yan Ming,Xu Xiangqin,Wu Huayin,Du Jinyin,Yu Jinhua,Mu Jinquan Archives of oral biology OBJECTIVES:Insulin-like growth factor 1 (IGF-1) is a broad-spectrum growth-promoting factor that plays a key role in natural tooth development. Human dental pulp stem cells (hDPSCs) are multipotent and can influence the reparative regeneration of dental pulp and dentin. This study was designed to evaluate the effects of IGF-1 on the proliferation and differentiation of human dental pulp stem cells. METHODS:HDPSCs were isolated and purified from human dental pulps. The proliferation and osteo/odontogenic differentiation of hDPSCs treated with 100ng/ml exogenous IGF-1 were subsequently investigated. RESULTS:MTT assays revealed that IGF-1 enhanced the proliferation of hDPSCs. ALP activity in IGF-1-treated group was obviously enhanced compared to the control group from days 3 to 9. Alizarin red staining revealed that the IGF-1-treated cells contained a greater number of mineralization nodules and had higher calcium concentrations. Moreover, western blot and qRT-PCR analyses demonstrated that the expression levels of several osteogenic genes (e.g., RUNX2, OSX, and OCN) and an odontoblast-specific marker (DSPP) were significantly up-regulated in IGF-1-treated hDPSCs as compared with untreated cells (P<0.01). Interestingly, the expression of phospho-ERK and phospho-p38 were also up-regulated, indicating that the MAPK signaling pathway is activated during the differentiation of hDPSCs. CONCLUSIONS:IGF-1 can promote the proliferation and osteo/odontogenic differentiation of hDPSCs by activating MAPK pathways. 10.1016/j.archoralbio.2016.08.011
    IGF-1 Mediates EphrinB1 Activation in Regulating Tertiary Dentin Formation. Matsumura S,Quispe-Salcedo A,Schiller C M,Shin J S,Locke B M,Yakar S,Shimizu E Journal of dental research Eph receptors belong to a subfamily of receptor tyrosine kinases that are activated by membrane-spanning ligands called ephrins. Previously, we demonstrated that the ephrinB1-EphB2 interaction regulates odontogenic/osteogenic differentiation from dental pulp cells (DPCs) in vitro. The goal of this study was to identify the molecular mechanisms regulated by the EphB2/ephrinB1 system that govern tertiary dentin formation in vitro and in vivo. During tooth development, ephrinB1, and EphB2 were expressed in preodontoblast and odontoblasts at postnatal day 4. EphrinB1 was continuously expressed in odontoblasts and odontoblastic processes until the completion of tooth eruption. In addition, ephrinB1 was expressed in odontoblastic processes 2 wk following tooth injury without pulp exposure, whereas EphB2 was expressed in the center of pulp niches but not odontoblasts. In a model of tooth injury with pulp exposure, ephrinB1 was strongly expressed in odontoblasts 4 wk postinjury. In vitro studies with human and mouse DPCs treated with calcium hydroxide (CH) or mineral trioxide aggregate (MTA) showed an increased expression of insulin-like growth factor 1 (IGF-1). Experiments using several inhibitors of IGF-1 receptor signaling revealed that inhibiting the Ras/Raf-1/MAPK pathway inhibited EphB2 expression, and inhibiting the PI3K/Akt/mTOR pathway specifically inhibited ephrinB1 gene expression. Tooth injury in mice with odontoblast-specific IGF-1 receptor ablation exhibited a reduced tertiary dentin volume, mineral density, and ephrinB1 expression 4 wk following injury. We conclude that the IGF-1/ephrinB1 axis plays significant roles in the early stages of tooth injury. Further research is needed to fully understand the potential of targeting ephrinB1 as a regenerative pulp therapy. 10.1177/0022034517708572
    The Role of GH/IGF Axis in Dento-Alveolar Complex from Development to Aging and Therapeutics: A Narrative Review. Koffi Kouassi Armel,Doublier Sophie,Ricort Jean-Marc,Babajko Sylvie,Nassif Ali,Isaac Juliane Cells The GH/IGF axis is a major regulator of bone formation and resorption and is essential to the achievement of normal skeleton growth and homeostasis. Beyond its key role in bone physiology, the GH/IGF axis has also major pleiotropic endocrine and autocrine/paracrine effects on mineralized tissues throughout life. This article aims to review the literature on GH, IGFs, IGF binding proteins, and their respective receptors in dental tissues, both epithelium (enamel) and mesenchyme (dentin, pulp, and tooth-supporting periodontium). The present review re-examines and refines the expression of the elements of the GH/IGF axis in oral tissues and their in vivo and in vitro mechanisms of action in different mineralizing cell types of the dento-alveolar complex including ameloblasts, odontoblasts, pulp cells, cementoblasts, periodontal ligament cells, and jaw osteoblasts focusing on cell-specific activities. Together, these data emphasize the determinant role of the GH/IGF axis in physiological and pathological development, morphometry, and aging of the teeth, the periodontium, and oral bones in humans, rodents, and other vertebrates. These advancements in oral biology have elicited an enormous interest among investigators to translate the fundamental discoveries on the GH/IGF axis into innovative strategies for targeted oral tissue therapies with local treatments, associated or not with materials, for orthodontics and the repair and regeneration of the dento-alveolar complex and oral bones. 10.3390/cells10051181
    Bone resorption deficiency affects tooth root development in RANKL mutant mice due to attenuated IGF-1 signaling in radicular odontoblasts. Huang Hong,Wang Jue,Zhang Yan,Zhu Guochun,Li Yi-Ping,Ping Ji,Chen Wei Bone The tooth root is essential for normal tooth physiological function. Studies on mice with mutations or targeted gene deletions revealed that osteoclasts (OCs) play an important role in tooth root development. However, knowledge on the cellular and molecular mechanism underlying how OCs mediate root formation is limited. During bone formation, growth factors (e.g. Insulin-like growth factor-1, IGF-1) liberated from bone matrix by osteoclastic bone resorption stimulate osteoblast differentiation. Thus, we hypothesize that OC-osteoblast coupling may also apply to OC-odontoblast coupling; therefore OCs may have a direct impact on odontoblast differentiation through the release of growth factor(s) from bone matrix, and consequently regulate tooth root formation. To test this hypothesis, we used a receptor activator of NF-κB ligand (RANKL) knockout mouse model in which OC differentiation and function was entirely blocked. We found that molar root formation and tooth eruption were defective in RANKL mice. Disrupted elongation and disorganization of Hertwig's epithelial root sheath (HERS) was observed in RANKL mice. Reduced expression of nuclear factor I C (NFIC), osterix, and dentin sialoprotein, markers essential for radicular (root) odontogenic cell differentiation indicated that odontoblast differentiation was disrupted in RANKL deficient mice likely contributing to the defect in root formation. Moreover, down-regulation of IGF/AKT/mTOR activity in odontoblast indicated that IGF signaling transduction in odontoblasts of the mutant mice was impaired. Treating odontoblast cells in vitro with conditioned medium from RANKL OCs cultured on bone slices resulted in inhibition of odontoblast differentiation. Moreover, depletion of IGF-1 in bone resorption-conditioned medium (BRCM) from wild-type (WT) OC significantly compromised the ability of WT osteoclastic BRCM to induce odontoblast differentiation while addition of IGF-1 into RANKL osteoclastic BRCM rescued impaired odontoblast differentiation, confirming that root and eruption defect in RANKL deficiency mice may result from failure of releasing of IGF-1 from bone matrix through OC bone resorption. These results suggest that OCs are important for odontoblast differentiation and tooth root formation, possibly through IGF/AKT/mTOR signaling mediated by cell-bone matrix interaction. These findings provide significant insights into regulatory mechanism of tooth root development, and also lay the foundation for root regeneration studies. 10.1016/j.bone.2017.12.026
    [Effect of growth hormone on osteopontin expression during orthodontic tooth movement in rats]. Ju Hualong,Cai Xiuying Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences OBJECTIVE:To investigate the effect of growth hormone on osteopontin expression during orthodontic tooth movement in rats.
 Methods: Forty male Wistar rats (2 weeks, average weight 200 g) were randomly divided into a control group and an experimental group (n=20 per group). The experimental group received subcutaneous injections of growth hormone at a dose of 0.15 U/(kg.d), and the control group received equivalent volumes of saline. A nickel-titanium spring was fixed between the maxillary incisors and the left upper first molar with a force of 0.49 N to move the molar mesially. All rats were sacrificed on day 3, 7, 10 or 14 with cardiac perfusion. And the left side of upper jaw was removed. The longitudinal section of the first molar was prepared from sagittal direction to observe osteopontin expression in the pressure area between the mesial buccal root and distal buccal root by immunohistochemical staining and semi-quantitative analysis.
 Results: The positive expression of osteopontin in the 2 groups showed similar trend, which was increased firstly and then was decreased. The expression of osteopontin on day 7 in the experimental group showed strong positive expression but it was decreased significantly on day 10 compared with the control group (P<0.05).
 Conclusion: Systemic application of growth hormone could affect the expression of osteopontin and probably plays an important role in regulating bone resorption in the compression area during orthodontic tooth movement in rats. 10.11817/j.issn.1672-7347.2017.09.007
    Duplication of the Pituitary Gland (DPG)-Plus Syndrome Associated With Midline Anomalies and Precocious Puberty: A Case Report and Review of the Literature. Prezioso Giovanni,Petraroli Maddalena,Bergonzani Michela,Davino Giusy,Labate Marialuisa,Ormitti Francesca,Anghinoni Marilena,Sesenna Enrico,Esposito Susanna Frontiers in endocrinology Duplication of the pituitary gland (DPG)-plus syndrome is a very rare developmental disorder with few cases described in the literature and characterized by multiple midline and central nervous system malformations. The hypothalamus and hypophysis involvement may be clinically associated with endocrine abnormalities. A 5.9-year-old female child was admitted to our Clinic for premature thelarche and acceleration of growth. DPG-plus syndrome with paired infundibula and pituitary glands was diagnosed after birth, when she appeared small for gestational age and she presented with lingual hypoplasia, cleft palate, right choanal stenosis, nasopharyngeal teratoma, and facial dysmorphisms. Neuroimaging revealed a duplication of the infundibula, the pituitary gland, and the dens of the epistropheus despite surgical removal of a rhino-pharyngeal mass performed at the age of two months. An array-CGH revealed a 2p12 deletion. At our evaluation, bone age assessment resulted advanced and initial pubertal activation was confirmed by Gonadotropin-Releasing Hormone stimulation test. Hormonal suppression treatment was started with satisfactory results. This case shows that DPG-plus syndrome must be considered in presence of midline and craniofacial malformations and endocrinological evaluations should be performed for the prompt and appropriate management of pubertal anomalies. 10.3389/fendo.2021.685888
    Childhood body mass index is associated with early dental development and eruption in a longitudinal sample from the Iowa Facial Growth Study. Nicholas Christina L,Kadavy Kevan,Holton Nathan E,Marshall Teresa,Richter Andrew,Southard Thomas American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics INTRODUCTION:Children with high body mass index (BMI) values have been demonstrated to have precocious dental development. Research has largely focused on cross-sectional data sets, leaving an incomplete understanding of the longitudinal relationship between BMI and dental maturation. METHODS:We used a pure longitudinal growth series to examine the relationship between dental development and childhood BMI. Periapical radiographs from 77 children from the Iowa Growth Study were used to estimate dental development for those with high BMI values. RESULTS:We confirmed prior studies in finding that children with higher BMI values were more likely to have advanced dental development for their ages (P <0.001). BMI at age 4 years was predictive for the timing of dental development at age 12 (P = 0.052). The precocity of the rate of dental development accelerated across growth. Overall dental development scores also correlated with the age of dental eruption for the mandibular canines and first premolars (P <0.001). CONCLUSIONS:High BMI values at young ages predict advanced dental development at later times, suggesting a long-term effect of BMI on dental maturation and implying the need for earlier orthodontic interventions in obese children. These results corroborate those of previous studies, building further evidence that relatively early dental eruption is another consequence of childhood obesity. 10.1016/j.ajodo.2017.10.033
    Fluoride, Thyroid Hormone Derangements and its Correlation with Tooth Eruption Pattern Among the Pediatric Population from Endemic and Non-endemic Fluorosis Areas. Kumar Vaibhav,Chahar Puneet,Kajjari Shweta,Rahman Faizia,Bansal Deepak K,Kapadia Junaid Mh The journal of contemporary dental practice AIM:To comparatively evaluate the status of fluoride in the body with thyroid activity in the pediatric population of endemic fluorosis areas. The present study also attempted to elucidate whether any correlation exists between fluoride and thyroid hormone derangement with delayed tooth eruption. MATERIALS AND METHODS:A total of 400 pediatric subjects were included in the present study. All the patients were divided into two broad groups; groups A and B. Group A included 200 subjects who belonged to the endemic fluorosis area while Group B included remaining 200 subjects, who belonged to the fluorosis non-endemic area. Group B subjects were taken as control. Group A subjects were further divided into two study groups as follows: Group A1: 100 Pediatric subjects with dental fluorosis, and Group A 2: A total of one hundred pediatric subjects without dental fluorosis. Dean's index of fluorosis was calculated in all the patients. Blood samples were collected and were sent to a laboratory for assessment of thyroid hormone levels. All the results were subjected to statistical analysis by Statistical Package for the Social Sciences (SPSS) software. RESULTS:Mean thyroid stimulating hormone (TSH), water fluoride levels, urine fluoride levels and serum fluoride levels of subjects in group 1 were found to be significantly higher than that of subjects of group 2. Delayed tooth eruption was absent in subjects of group B while it was present in 100 subjects of group A. Thyroid hormone level derangement was seen in 54 percent subjects of group B, while it was seen in 67.5% subjects of group A. CONCLUSION:Positive correlation exists between fluorosis and thyroid functional activity. However; the tooth eruption pattern is independent up on the thyroid hormone derangement. CLINICAL SIGNIFICANCE:Delayed tooth eruption and alteration in thyroid hormone levels can occur in subjects of the endemic fluoride areas. Therefore, adequate measures should be taken for controlling such adverse effects.
    Vitamin D and Dental Caries in Children with Growth Hormone Deficiency. Wójcik Dorota,Szalewski Leszek,Pietryka-Michałowska Elżbieta,Borowicz Janusz,Pels Elżbieta,Beń-Skowronek Iwona International journal of endocrinology Vitamin D deficiency is a common risk factor for multifactorial diseases, and it seems to be associated with growth hormone deficiency (GHD). Vitamin D could prevent dental caries. The goal of this study was to identify whether there is an association between hormonal therapy with growth hormone (GH), vitamin D supplementation, vitamin D levels, and the occurrence of caries among children affected by GHD. The study group consisted of patients from the Department of Endocrinology and Diabetology of the University Paediatric Hospital at the Medical University of Lublin treated with recombinant human GH for pituitary GHD. It was conducted between October 2014 and June 2015. The study group included 121 children and adolescents aged 6 to 18 years, with 56 children from rural areas and 65 from urban areas. The study group was stratified by the area of residence. We found the statistically significant impact of vitamin D concentration on the average value of the DMFT (decayed, missed, and filled teeth) index and its component-DT (decayed teeth), which was noted in subjects from rural areas. Among patients from urban areas, we found a statistically significant correlation between duration of therapy and the DMFT index. An increase in duration of GH therapy by 10 months leads to a mean increase in DMFT index by 0.70. Based on multiple regression analysis, we developed the following model: value of DT = 3.10 - 0.73category of vitamin D concentration - 0.07duration of supplementation (in months). In this model, variables with a significant impact on the value of DT in the group of patients from rural areas include time of vitamin D supplementation and category of vitamin D concentration. Greater emphasis should be placed on promoting vitamin D as a potentially effective agent reducing the number of dental caries, especially among patients with GHD. 10.1155/2019/2172137
    Parathyroid hormone-related peptide (1-34) promotes tooth eruption and inhibits osteogenesis of dental follicle cells during tooth development. Zhang Jiawei,Liao Lijun,Li Yuyu,Xu Yang,Guo Weihua,Tian Weidong,Zou Shujuan Journal of cellular physiology Dental follicle cells (DFCs) activate and recruit osteoclasts for tooth development and tooth eruption, whereas DFCs themselves differentiate into osteoblasts to form alveolar bone surrounding tooth roots through the interaction with Hertwig's epithelial root sheath (HERS). Also during tooth development, parathyroid hormone-related peptide (PTHrP) is expressed surrounding the tooth germ. Thus, we aimed to investigate the effect of PTHrP (1-34) on bone resorption and osteogenesis of DFCs in vitro and in vivo. In vitro studies demonstrated that DFCs cocultured with HERS cells expressed higher levels of BSP and OPN than the DFCs control group, whereas cocultured DFCs treated with PTHrP (1-34) had lower expressions of ALP, RUNX2, BSP, and OPN than the cocultured DFCs control group. Moreover, we found PTHrP (1-34) inhibited osteogenesis of cocultured DFCs by inactivating the Wnt/β-catenin pathway. PTHrP (1-34) also increased the expression of RANKL/OPG ratio in DFCs. Consistently, in vivo study found that PTHrP (1-34) accelerated tooth eruption and inhibited alveolar bone formation. Therefore, these results suggest that PTHrP (1-34) accelerates tooth eruption and inhibits osteogenesis of DFCs by inactivating Wnt/β-catenin pathway. 10.1002/jcp.27857
    Effect of growth hormone treatment on craniofacial growth in children: Idiopathic short stature versus growth hormone deficiency. Choi Sung-Hwan,Fan Dong,Hwang Mi-Soo,Lee Hee-Kyung,Hwang Chung-Ju Journal of the Formosan Medical Association = Taiwan yi zhi BACKGROUND/PURPOSE:Few studies have evaluated craniofacial growth in boys and girls with idiopathic short stature (ISS) during growth hormone (GH) treatment. The aim of this study was to evaluate the effect of GH treatment on craniofacial growth in children with ISS, compared with those with growth hormone deficiency (GHD). METHODS:This study included 36 children (mean age, 11.3 ± 1.8 years) who were treated with GH consecutively. Lateral cephalograms were analyzed before and 2 years after start of GH treatment. RESULTS:There were no significant differences in age and sex between ISS and GHD groups and the reference group from semilongitudinal study (10 boys and 8 girls from each group). Before treatment, girls with ISS showed a skeletal Class II facial profile compared with the GHD and reference groups (p = 0.003). During GH treatment, the amount of maxillary length increased beyond norm in the ISS and GHD groups in boys (p = 0.035) > 3 standard deviation score (SDS). Meanwhile, mandibular ramus height (p = 0.001), corpus length, and total mandibular length (p = 0.007 for both) increased more in girls with ISS than in girls with GHD. Lower and total anterior facial heights increased more in girls with ISS than in girls with GHD (p = 0.021 and p = 0.007, respectively), > 7-11 SDS. CONCLUSION:GH should be administered carefully when treating girls with ISS, because GH treatment has great effects on vertical overgrowth of the mandible and can result in longer face. 10.1016/j.jfma.2016.05.011
    The rachitic tooth. Foster Brian L,Nociti Francisco H,Somerman Martha J Endocrine reviews Teeth are mineralized organs composed of three unique hard tissues, enamel, dentin, and cementum, and supported by the surrounding alveolar bone. Although odontogenesis differs from osteogenesis in several respects, tooth mineralization is susceptible to similar developmental failures as bone. Here we discuss conditions fitting under the umbrella of rickets, which traditionally referred to skeletal disease associated with vitamin D deficiency but has been more recently expanded to include newly identified factors involved in endocrine regulation of vitamin D, phosphate, and calcium, including phosphate-regulating endopeptidase homolog, X-linked, fibroblast growth factor 23, and dentin matrix protein 1. Systemic mineral metabolism intersects with local regulation of mineralization, and factors including tissue nonspecific alkaline phosphatase are necessary for proper mineralization, where rickets can result from loss of activity of tissue nonspecific alkaline phosphatase. Individuals suffering from rickets often bear the additional burden of a defective dentition, and transgenic mouse models have aided in understanding the nature and mechanisms involved in tooth defects, which may or may not parallel rachitic bone defects. This report reviews dental effects of the range of rachitic disorders, including discussion of etiologies of hereditary forms of rickets, a survey of resulting bone and tooth mineralization disorders, and a discussion of mechanisms, known and hypothesized, involved in the observed dental pathologies. Descriptions of human pathology are augmented by analysis of transgenic mouse models, and new interpretations are brought to bear on questions of how teeth are affected under conditions of rickets. In short, the rachitic tooth will be revealed. 10.1210/er.2013-1009
    Crown heights in the permanent teeth of 45,X and 45,X/46,XX females. Pentinpuro Raija Helena,Lähdesmäki Raija Eliisa,Niinimaa Ahti Olavi,Pesonen Paula Ritva Orvokki,Alvesalo Lassi Juhani Acta odontologica Scandinavica OBJECTIVE:Previous results regarding human sex chromosome aneuploidies have shown that the X and Y chromosomes affect tooth size and morphology. This study looked for the effect of sex chromosome deficiency on permanent tooth crown heights. MATERIALS AND METHODS:The material, from the Finnish KVANTTI Research Project, consisted of 97 45,X females and 15 45,X/46,XX females. The controls were 32 sisters and 28 mothers of the 45,X females, eight sisters and two mothers of the 45,X/46,XX females and 35 female population controls. Crown heights of all the available teeth except third molars on both sides of the jaws were measured from panoramic radiographs with a digital calliper according to the defined procedure. RESULTS:The tooth crown heights were significantly smaller in the 45,X females than in the female population controls, except for the incisors and one canine in the maxilla, whereas the tooth crown heights of the 45,X/46,XX females were close to those of the normal control females. The differences between the 45,X and 45,X/46,XX females were statistically significant, excluding the upper incisor area and a few teeth in the mandible. CONCLUSIONS:The effect of the sex chromosome deficiency on permanent tooth crown height is due to the magnitude of lacking sex chromosome material. The present results regarding the 45,X females are parallel to previous findings in Turner patients regarding reduced mesiodistal and labiolingual dimensions and tooth crown heights in the permanent dentition. 10.3109/00016357.2014.921327
    [The mouth of patients with acromegaly]. Cortet-Rudelli Christine Presse medicale (Paris, France : 1983) Orofacial changes are frequent in acromegaly. Their evolution is slowly progressive. The lips (everted and thickened), the mandibular morphology (prognathism), the tongue (macroglossia), the soft palate and the uvula (increased and thickened), the parodontis (gingival hyperplasia, paradontitis), the teeth (increased interdental spaces, hypercementosis, increased dental mobility, multiple tooth loss) are concerned. Functional consequences are significant (obstructive sleep apnea syndrome, malocclusion, pain of the oral maxillofacial area, decrease of the quality of life). They are rarely noticed as the first symptoms of the disease and rarely responsible for the diagnosis of acromegaly because of a progressive development over a long period of time, and because of the low prevalence of the disease which can be unknown by dentists and dental surgeons. When patients are cured or well-controlled, abnormalities of soft tissues improve but are not always completely reversible and bone enlargement remain unchanged. If any corrective surgical procedures are to be performed, this should be carried out only after normalization of GH and IGF I levels. 10.1016/j.lpm.2017.09.001
    Familial dysalbuminemic hyperthyroxinemia in a 4-year-old girl with hyperactivity, palpitations and advanced dental age: how gold standard assays may be misleading. Choudhary Abha,Sriphrapradang Chutintorn,Refetoff Samuel,Antal Zoltan Journal of pediatric endocrinology & metabolism : JPEM Here we report the case of a young girl who had vague signs and symptoms potentially attributable to hyperthyroidism and was found to have autoimmune thyroiditis and hyperthyroxinemia. The elevated serum free thyroxine levels were persistent when measured by both standard assays and equilibrium dialysis/high-pressure liquid chromatography-tandem mass spectrometry. The clinical symptoms, with discordant thyroid test results, created a diagnostic dilemma that led initially to unnecessary additional evaluations. She was ultimately found to have familial dysalbuminemic hyperthyroxinemia (FDH) and required no therapy. This case highlights the inherent difficulties in evaluating children, who typically have vague signs and symptoms of thyroid dysfunction, when, in addition, they have an unrelated acquired (autoimmune) as well as a genetic (FDH) defect. The benefit of including testing for immediate members of the family is emphasized. 10.1515/jpem-2014-0019
    CHANGES IN TOOTH HARD TISSUE MINERALI-ZATION AND BLOOD RHEOLOGY IN HEALTHY ADOLESCENTS AND THOSE WITH THYROID DYSFUNCTION. Beriashvili S,Nikolaishvili M,Mantskava M,Momtsemlidze N,Franchuk K Georgian medical news Thyroid dysfunction causes spreading and development of caries in the teeth and changes in periodontal tissues. In addition, it causes changes in peripheral blood flow and mineralization, local transcapillary metabolism causes changes in blood rheology. There are only few works in this direction and, therefore, the purpose of our research was to find out how the mineralization and the rheological properties of blood are changed in lesion of periodontal tissue on a background of thyroid dysfunction. Accordingly, the stomatological study was conducted in 75 adolescents aged 12-18 years by the standard method, recommended by the World Health Organization. According to the study, 45 patients out of them suffered from thyroid dysfunction, in particular from hypothyroidism. The comparator group consisted of 30 children of the same age without endocrine abnormalities. By the gained results it is noted that in spite of different type lesions due to dental caries, the caries incidence and intensiveness is higher in children with hypothyroidism as compared to healthy children. Decrease in saliva excretion rate and increase in oral fluid viscosity was found in children with thyroid and endocrine diseases as compared to healthy children. In children with endocrine disorders concurrent increase in calcium content (1,43±0,08 mmol/l) and decrease in inorganic phosphate concentrations (4,54±0,15 mmol/l) is reliably established. In children with thyroid disfunction and while periodontal tissue pathology, rheological features are disordered more dramatically than in healthy children. Therefore, it can be said that the changes in the adolescents' thyroid function is one of the reasons for formation of periodontal tissue diseases.Therefore, at detecting even the first signs of the periodontal tissue diseases, it is desirable in adolescents to assess the thyroid functional condition, since it will be the precondition for effective treatment and management of dental disease, in particular, dental caries and lesions of periodontal tissue.
    Estrogen and bisphenol A affect male rat enamel formation and promote ameloblast proliferation. Jedeon Katia,Loiodice Sophia,Marciano Clémence,Vinel Alexia,Canivenc Lavier Marie-Chantal,Berdal Ariane,Babajko Sylvie Endocrinology Bisphenol A (BPA) is a widespread endocrine disrupting chemical (EDC) strongly suspected to have adverse health effects. Numerous tissues and cells are affected by BPA, and we showed recently that BPA targets include ameloblasts and enamel. We therefore investigated the effects of BPA on ameloblasts and the possible involvement of the estrogen signaling pathway. Rats were exposed daily to low-dose BPA, and developed enamel hypomineralization similar to human molar incisor hypomineralization (MIH). BPA increased ameloblast proliferation in vivo and in vitro. The proliferation of the rat dental epithelial cell line HAT-7 was also increased by estrogen (E2). Ameloblasts express ERα but not ERβ both in vivo and in vitro. The ER antagonist ICI 182,780 was used to inactivate ERα and abolished the effects of E2 on cell proliferation and transcription, but only partially reduced the effects of BPA. In conclusion, we show, for the first time, that: 1) BPA has ER-dependent and ER-independent effects on ameloblast proliferation and gene transcription; 2) the estrogen signaling pathway is involved in tooth development and the enamel mineralization process; and 3) BPA impacts preferentially amelogenesis in male rats. These results are consistent with the steroid hormones having effect on ameloblasts, raising the issues of the hormonal influence on amelogenesis and possible differences in enamel quality between sexes. 10.1210/en.2013-2161
    Clinical and molecular findings in 39 patients with KBG syndrome caused by deletion or mutation of ANKRD11. Goldenberg Alice,Riccardi Florence,Tessier Aude,Pfundt Rolph,Busa Tiffany,Cacciagli Pierre,Capri Yline,Coutton Charles,Delahaye-Duriez Andree,Frebourg Thierry,Gatinois Vincent,Guerrot Anne-Marie,Genevieve David,Lecoquierre Francois,Jacquette Aurélia,Khau Van Kien Philippe,Leheup Bruno,Marlin Sandrine,Verloes Alain,Michaud Vincent,Nadeau Gwenael,Mignot Cyril,Parent Philippe,Rossi Massimiliano,Toutain Annick,Schaefer Elise,Thauvin-Robinet Christel,Van Maldergem Lionel,Thevenon Julien,Satre Véronique,Perrin Laurence,Vincent-Delorme Catherine,Sorlin Arthur,Missirian Chantal,Villard Laurent,Mancini Julien,Saugier-Veber Pascale,Philip Nicole American journal of medical genetics. Part A KBG syndrome, due to ANKRD11 alteration is characterized by developmental delay, short stature, dysmorphic facial features, and skeletal anomalies. We report a clinical and molecular study of 39 patients affected by KBG syndrome. Among them, 19 were diagnosed after the detection of a 16q24.3 deletion encompassing the ANKRD11 gene by array CGH. In the 20 remaining patients, the clinical suspicion was confirmed by the identification of an ANKRD11 mutation by direct sequencing. We present arguments to modulate the previously reported diagnostic criteria. Macrodontia should no longer be considered a mandatory feature. KBG syndrome is compatible with autonomous life in adulthood. Autism is less frequent than previously reported. We also describe new clinical findings with a potential impact on the follow-up of patients, such as precocious puberty and a case of malignancy. Most deletions remove the 5'end or the entire coding region but never extend toward 16q telomere suggesting that distal 16q deletion could be lethal. Although ANKRD11 appears to be a major gene associated with intellectual disability, KBG syndrome remains under-diagnosed. NGS-based approaches for sequencing will improve the detection of point mutations in this gene. Broad knowledge of the clinical phenotype is essential for a correct interpretation of the molecular results. © 2016 Wiley Periodicals, Inc. 10.1002/ajmg.a.37878
    Influence of human parathyroid hormone during orthodontic tooth movement and relapse in the osteoporotic rat model: A preliminary study. Lee H S,Heo H A,Park S H,Lee W,Pyo S W Orthodontics & craniofacial research OBJECTIVE:To investigate the effects of parathyroid hormone (PTH) on tooth movement in ovariectomized (OVX) rats by comparing the tooth movement distance and relapse and by examining the alveolar bone microstructure. MATERIALS AND METHODS:Thirty 8-week-old female rats were classified into 3 groups: sham-operated, OVX and ovariectomized rats injected with PTH (PTH). Eight weeks later, a closed-coil spring appliance was placed between the maxillary incisor and the first molar and then activated with 50 cN of force. During tooth movement, 30 μg/kg of PTH was administered 3 times per week in the PTH group. Tooth movement distances were measured weekly. Five rats in each group were killed after 3 weeks for microcomputerized tomographic analysis, and the remaining 5 rats in each group were killed at an additional 3 weeks after the removal of the appliance to measure relapsed distance. RESULTS:The OVX group showed significantly greater tooth movement compared to those in the other 2 groups at 2 and 3 weeks (P < .05). The relapse distance and relapse percentage for the OVX group were higher; however, it did not differ significantly from the PTH group. On micro-CT analysis, bone volume/tissue volume ratio and bone mineral density in the PTH group were significantly greater than in the OVX group (P < .05). CONCLUSIONS:Application of PTH did not promote tooth movement in OVX rat, however, did lead to decrease in relapse tendency. Therefore, the application of PTH during orthodontic treatment of patients with osteoporosis should be carefully considered. 10.1111/ocr.12226
    Twenty-year follow-up of a familial case of PTH1R-associated primary failure of tooth eruption. Kanno Cláudia Misue,de Oliveira José Américo,Garcia José Fernando,Roth Helmut,Weber Bernhard H F American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics INTRODUCTION:Nonsyndromic primary failure of eruption (PFE) is a rare autosomal dominant disorder of dental eruption with no obvious dental or soft tissue interference. The purposes of this study were to genetically and clinically characterize a family with many members affected by PFE and to describe the natural evolution of the disorder. METHODS:Three generations of a family with 18 members, 10 of them clinically affected by PFE, were evaluated periodically during 20 years of clinical follow-up. PFE was observed in varying degrees of severity in both sexes. Clinical presentation became more severe in adulthood. One patient had spontaneous reeruption of 2 posterior teeth. Cervical root resorptions were observed in 3 members. Genetic analysis showed a deleterious heterozygous mutation in intron 9 of the PTH1R gene (c.639-2A>G) and diagnosed an additional affected member. CONCLUSIONS:The long-term follow-up of PFE cases in this family permitted the following observations: (1) the onset occurred from the preemergence to the postemergence phases, (2) PFE appeared to be closely related to ankylosis, (3) affected teeth maintained the eruptive potential even in adulthood, (4) the earlier the onset the more severe the open bite, and (5) cervical root resorptions occurred in 3 affected members. 10.1016/j.ajodo.2016.09.012
    Influence of growth hormone therapy on selected dental and skeletal system parameters. Partyka Małgorzata,Chałas Renata,Dunin-Wilczyńska Izabella,Drohomyretska Myroslava,Klatka Maria Annals of agricultural and environmental medicine : AAEM INTRODUCTION:Growth hormone deficiency (GHD) is one of the main indications for growth hormone therapy. One characteristic of this disease is bone age delay in relation to the chronological age. Pituitary dysfunction negatively affects the growth and development of the jaws and teeth of the child. The secretion of endocrine glands regulates growth, development, and gender differentiation. It also controls the growth of bones and teeth, regulates metabolism of calcium and phosphate, proteins, lipids and carbohydrates. The primary role in the endocrine system is played by the pituitary gland which is responsible for the production of somatotropin [1]. Dysfunction of the pituitary gland has a negative effect on the growth and development of long bones in the body, and may have an adverse effect on the development of maxilla, mandible and dentition of a child. There is some information in the literature that dental age is delayed in short stature children; the replacement of deciduous teeth by permanent teeth is also delayed, and newly erupted permanent teeth often require orthodontic treatment. Applying hormonal therapy positively affects the process of replacement of dentition [2, 3, 4, 5, 6]. OBJECTIVES:The aim of the study was to assess bone and dental age, as well as analyze the state of dentition in children diagnosed with GH deficiency treated with growth hormone, depending on the duration of treatment. MATERIAL AND METHODS:The study material consisted of 110 children (27 males, 83 females), hospitalized for somatotropin hypopituitarism in the Department of Paediatric Endocrinology and Diabetology at the Medical University of Lublin, Poland. The mean birth age was 13 years (156 months) with a standard deviation of 2 years and 6 months (30 months). 47 children (43%) started treatment with the growth hormone (group starting treatment) and 63 children (57%) whose treatment was started 2-3 years previously (group in the course of treatment). The control group consisted of 41 generally healthy children (15males, 25 females) with ENT problems, such as hypoacusis and a condition after nasal injury, hospitalized in the Department of Paediatric Otolaryngology at the Medical University of Lublin, Poland. The mean age was 11 years and 5 months (137 months) with standard deviation of 2 years and 5 months (29 months). Informed consent was obtained from the parents. The study was approved by the Bioethical Committee at the Medical University of Lublin (Resolution No. KE-0254 /216 /2012). 10.5604/12321966.1233573
    Multiple impacted permanent teeth, an indicator for early detection of hypoparathyroidism: A rare case report. Reddy G Santosh,Chalapathi K V,Reddy D Santhosh,Rana Subhrajit,Kalyan M,Kartheeki B,Nayyar Abhishek Singh Journal of family medicine and primary care Eruption is a process of continuous movement of the developing tooth bud from its developmental location to functional location. Teeth that cease to erupt before emergence to their functional position in the oral cavity are termed as impactions. In permanent dentition, third molars are the most frequently impacted teeth followed by the canines. When impaction involves few teeth, the condition is localized but when it involves multiple teeth, the condition becomes generalized and is often associated with some derangement of the normal physiological processes. Factors causing impactions may be localized, pertaining to the area or, systemic or, generalized including bone disorders such as cleidocranial dysplasia and/or some sort of endocrinological disturbance such as hypoparathyroidism. Hypoparathyroidism is a rare endocrinological disorder accompanied by anomalies of various systems including bones and teeth. The dental defects due to hypoparathyroidism may present as hypocalcemia, aplasia and/or hypoplasia, defects of mineralization, short and blunted roots, delayed eruptions, and clinically missing or impacted teeth. This report describes an interesting and unusual case where multiple impacted permanent teeth and retained primary teeth accompanied by other clinical manifestations in a 16-year-old female patient probed the clinicians for further investigations which, eventually, aided in early diagnosis of hypoparathyroidism. 10.4103/jfmpc.jfmpc_352_17
    Congenital adrenal hyperplasia: a case report with premature teeth exfoliation and bone resorption. Angelopoulou Matina V,Kontogiorgos Elias,Emmanouil Dimitris Pediatrics Congenital adrenal hyperplasia (CAH) is an inherited autosomal recessive disorder characterized by insufficient production of cortisol. The aim of this case report was to present a child with CAH, premature exfoliation of primary teeth and accelerated eruption of his permanent teeth related to bone resorption. A 4.5-year-old Caucasian boy with CAH and long-term administration of glucocorticoids was referred for dental restoration. Clinical examination revealed primary molars with worn stainless steel crowns, severe attrition of the upper canines, and absence of the upper incisors. Before the completion of treatment, abnormal mobility of the first upper primary molars and the lower incisors was detected, and a few days later the teeth exfoliated prematurely. Histologic examination revealed normal tooth structure. Alkaline phosphatase and blood cells values were normal. Eruption of the permanent dentition was also accelerated. Tooth mobility was noticed in the permanent teeth as soon as they erupted, along with bone destruction. Examination revealed an elevated level of receptor activator of nuclear factor-κB ligand and lower-than-normal osteoprotegerin and vitamin D levels. The patient was treated with vitamin D supplements, and his teeth have been stable ever since. CAH is a serious chronic disorder appearing in children with accelerated dental development and possibly premature loss of primary teeth. 10.1542/peds.2014-3577
    4H syndrome with late-onset growth hormone deficiency caused by POLR3A mutations. Potic Ana,Brais Bernard,Choquet Karine,Schiffmann Raphael,Bernard Geneviève Archives of neurology OBJECTIVE:To report a novel clinical and genetic presentation of a patient with 4H syndrome, which is a recently described leukodystrophy syndrome characterized by ataxia, hypomyelination, hypodontia, and hypogonadotropic hypogonadism. DESIGN:Case report. SETTING:University teaching hospital. PATIENT:A 20-year-old male patient with 4H syndrome. RESULTS:The patient was found to have delayed tooth eruption and a late-onset growth hormone deficiency without overt growth failure. He was a compound heterozygote for the novel missense mutations R1005H and A1331T of POLR3A, which codes for the largest subunit of RNA polymerase III. CONCLUSION:This is the first report of this type of leukodystrophy from southeastern Europe, which suggests that POLR3A mutations should be suspected in patients with hypomyelination and various central nervous system–based endocrine abnormalities. 10.1001/archneurol.2011.1963
    Craniofacial morphology and dental maturity in children with reduced somatic growth of different aetiology and the effect of growth hormone treatment. Davidopoulou Sotiria,Chatzigianni Athina Progress in orthodontics Children with reduced somatic growth may present various endocrinal diseases, especially growth hormone deficiency (GHD), idiopathic short stature (ISS), chromosomal aberrations, or genetic disorders. In an attempt to normalize the short stature, growth hormone (GH) is administered to these children. The aim of this literature review was to collect information about the craniofacial morphology and dental maturity in these children and to present the existing knowledge on the effect of GH treatment on the above structures.This review demonstrated that regardless of the origin of the somatic growth retardation, these children show similar craniofacial features, such as short length of the cranial base and the mandible, increased lower facial height, retropositioned mandible, and obtuse gonion angle. On the other hand, dental maturation does not demonstrate a specific pattern. Except for the above findings, muscle alterations seem to be present in individuals with short stature, who present low body muscle mass and strength, while studies on their craniofacial muscles seem to be lacking. After GH administration, the exact amount and pattern of craniofacial growth is unpredictable; however, the facial convexity decreases, mandibular length increases, and posterior facial height increases, while tooth eruption remains unaffected. Thus, it is of great importance to gain more insight into the craniofacial growth of treated and untreated children with reduced somatic growth so that the influence of GH therapy on the various craniofacial structures could be ascertained and proper orthodontic treatment could be selected. 10.1186/s40510-017-0164-2
    Constitutively active PTH/PTHrP receptor in odontoblasts alters odontoblast and ameloblast function and maturation. Calvi L M,Shin H I,Knight M C,Weber J M,Young M F,Giovannetti A,Schipani E Mechanisms of development Parathyroid hormone (PTH)-related protein (PTH-rP) is an important autocrine/paracrine attenuator of programmed cell differentiation whose expression is restricted to the epithelial layer in tooth development. The PTH/PTHrP receptor (PPR) mRNA in contrast is detected in the dental papilla, suggesting that PTHrP and the PPR may modulate epithelial-mesenchymal interactions. To explore the possible interactions, we studied the previously described transgenic mice in which a constitutively active PPR is targeted to osteoblastic cells. These transgenic mice have a vivid postnatal bone and tooth phenotype, with normal tooth eruption but abnormal, widened crowns. Transgene mRNA expression was first detected at birth in the dental papilla and, at 1 week postnatally, in odontoblasts. There was no transgene expression in ameloblasts or in other epithelial structures. Prenatally, transgenic molars and incisors revealed no remarkable change. By the age of 1 week, the dental papilla was widened, with disorganization of the odontoblastic layer and decreased dentin matrix. In addition, the number of cusps was abnormally increased, the ameloblastic layer disorganized, and enamel matrix decreased. Odontoblastic and, surprisingly, ameloblastic cytodifferentiation was impaired, as shown by in situ hybridization and electron microscopy. Interestingly, ameloblastic expression of Sonic Hedgehog, a major determinant of ameloblastic cytodifferentiation, was dramatically altered in the transgenic molars. These data suggest that odontoblastic activation of the PPR may play an important role in terminal odontoblastic and, indirectly, ameloblastic cytodifferentiation, and describe a useful model to study how this novel action of the PPR may modulate mesenchymal/epithelial interactions at later stages of tooth morphogenesis and development. 10.1016/j.mod.2004.02.004
    Clinical Implications of Growth Hormone Deficiency for Oral Health in Children: A Systematic Review. Torlińska-Walkowiak Natalia,Majewska Katarzyna Anna,Kędzia Andrzej,Opydo-Szymaczek Justyna Journal of clinical medicine Growth hormone (GH) is involved in the regulation of the postnatal dental and skeletal growth, but its effects on oral health have not been clearly defined. This paper aims to provide a review of current clinical knowledge of dental caries, tooth wear, developmental enamel defects, craniofacial growth and morphology, dental maturation, and tooth eruption in growth hormone deficient (GHD) children. A systematic review was carried out using Scopus, MEDLINE-EbscoHost and Web of Science from 2000 to May 2021. PRISMA guidelines for reporting systematic reviews were followed. All the selected studies involved groups under eighteen years of age, covering a total of 465 GHD patients. The studies that were selected provide reliable evidence for delayed dental maturity and orthodontic disturbances in GHD patients. Data on dental hard tissues pathology are scarce and are limited to occurrences of dental caries. GHD children showed abnormal craniofacial morphology with reduced mandibular dimensions, with a resulting tendency towards Angle's Class II occlusion, which affected up to 31% of patients. Dental age has been shown to be delayed in GHD patients by about 1 to 2 years. Moreover, the risk of dental caries in children with GHD decreases with increasing levels of vitamin D. Hence, further studies would be valuable for evaluating the risk of various oral health problems and to organize targeted dental care for this vulnerable group. 10.3390/jcm10163733
    Dental findings in the diagnosis of idiopathic hypoparathyroidism. Kamarthi Nagaraju,Venkatraman Sreenivasan,Patil Prashant Bhimrao Annals of Saudi medicine Idiopathic hypoparathyroidism (IHP) is a rare endocrinopathy, characterized by the disturbances in calcium and phosphorous metabolism, owing to deficiency in parathyroid hormone, which leads to tetanic manifestations. Onset of the clinical features occurs early in life, and the severity depends on the extent of chemical imbalance. This article describes a case of 22-year-old patient undiagnosed for 12 years with this endocrinopathy (IHP). Over retained deciduous teeth, delayed eruption, impacted tooth and short roots probably resulting from untreated hypocalcemia during the developmental phase of dentition enabled us to unearth this endocrinopathy through a series of investigations. Thus the article emphasizes the importance of dental findings of this endocrinopathy. 10.5144/0256-4947.2013.411
    Parathyroid hormone receptor signalling in osterix-expressing mesenchymal progenitors is essential for tooth root formation. Ono Wanida,Sakagami Naoko,Nishimori Shigeki,Ono Noriaki,Kronenberg Henry M Nature communications Dental root formation is a dynamic process in which mesenchymal cells migrate toward the site of the future root, differentiate and secrete dentin and cementum. However, the identities of dental mesenchymal progenitors are largely unknown. Here we show that cells expressing osterix are mesenchymal progenitors contributing to all relevant cell types during morphogenesis. The majority of cells expressing parathyroid hormone-related peptide (PTHrP) are in the dental follicle and on the root surface, and deletion of its receptor (PPR) in these progenitors leads to failure of eruption and significantly truncated roots lacking periodontal ligaments. The PPR-deficient progenitors exhibit accelerated cementoblast differentiation with upregulation of nuclear factor I/C (Nfic). Deletion of histone deacetylase-4 (HDAC4) partially recapitulates the PPR deletion root phenotype. These findings indicate that PPR signalling in dental mesenchymal progenitors is essential for tooth root formation, underscoring importance of the PTHrP-PPR system during root morphogenesis and tooth eruption. 10.1038/ncomms11277
    Parathyroid hormone intermittent administration promotes delay on rat incisor eruption. Silva M A D,Vasconcelos D F P,Marques M R,Barros S P Archives of oral biology OBJECTIVE:This study evaluated the influence of parathyroid hormone (PTH) (1-34) intermittent administration on rat eruption rates of lower incisors under normo, hyper and hypofunctional conditions, Sharpey fibers insertion, and alveolar bone formation. MATERIALS AND METHODS:Wistar male rats received PTH (1-34) three times a week during the entire experimental period, 31days. Control animals received the same concentration of the vehicle solution during the same period. Three injections of alizarin were also performed. The experiment evaluated the eruptive rate, the alveolar bone formation and also the morphology, and the area density of Sharpey fibers. After the sacrifice, the mandibles were dissected and samples were prepared for fluorescence and scanning electron microscopy observations. RESULTS:PTH-treated animals showed significantly reduced eruption rates in all different functional conditions. Analysis evidenced that PTH-treated rats present an increase in bone formation and area density of the Sharpey fibers. CONCLUSION:We concluded that the PTH (1-34) intermittent administration reduced the eruptive process rates, through bone formation enhancement and increase in the area density of Sharpey fibers. 10.1016/j.archoralbio.2016.05.017
    Thyroid Function during Early Life and Dental Development. Vucic S,Korevaar T I M,Dhamo B,Jaddoe V W V,Peeters R P,Wolvius E B,Ongkosuwito E M Journal of dental research Children with low levels of thyroid hormones (hypothyroidism) have delayed tooth eruption, enamel hypoplasia, micrognathia, and anterior open bite, whereas children with hyperthyroidism may suffer from accelerated tooth eruption, maxillary, and mandibular osteoporosis. However, it is still unknown whether thyroid function variations within the normal or subclinical range also have an impact on hard dental tissues in healthy children. The objective of this study was, therefore, to investigate the association between thyroid function from the fetal period until early childhood and dental development at school age. This study is embedded in the Generation R Study, a population-based cohort study established in Rotterdam, the Netherlands. Maternal thyroid function (thyroid-stimulating hormone [TSH], free thyroxine [FT4], and thyroid peroxidase antibody [TPOAb] concentrations) was measured during early pregnancy, and thyroid function of the offspring (TSH and FT4) was measured in cord blood at birth and in early childhood (6 y). Dental development was assessed from panoramic radiographs of children of school-going age (9 y). In total, 2,387 to 2,706 subjects were available for the multivariable linear regression analysis, depending on the point in time of thyroid function measurement. There was an inverse association between cord blood and early childhood TSH concentrations with dental development, with a -0.06 lower standard deviation (SD) per 1 mU/L of TSH (95% confidence interval [CI], -0.11 to -0.01) and a -0.06 lower SD per 1 mU/L of TSH (95% CI, -0.11 to 0.00), respectively. There was no association between the maternal thyroid function during pregnancy and the dental development score of the child. However, TPOAb-positive mothers had children with a -0.20 SD (adjusted 95% CI, -0.35 to -0.04) lower dental development score compared with TPOAb-negative mothers. The findings of this study suggest that the thyroid hormone is involved in the maturation of teeth from the early stages of life onward. 10.1177/0022034517708551
    Oral findings in DiGeorge syndrome: clinical features and histologic study of primary teeth. Fukui N,Amano A,Akiyama S,Daikoku H,Wakisaka S,Morisaki I Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics OBJECTIVE:For the purpose of supplementing the shortage of dental information about DiGeorge syndrome, we report two cases of the syndrome seen in Japanese boys. STUDY DESIGN:Two cases were compared with respect to orofacial and dental findings; one was a case of complete DiGeorge syndrome and the other a case of partial DiGeorge syndrome. Extracted deciduous teeth from the two boys underwent histologic study. RESULTS:Each patient showed systemic developmental delay, hypocalcemia, and slight mental retardation. In the orofacial area, hypertelorism, a short philtrum, thick and reflected lips, and hypoplasia of the nasopharynx were also observed. A dental examination showed delayed formation and eruption of permanent teeth, aplasia of the nasopharynx, and enamel hypoplasia along with enamel hypocalcification. Structural streaks with increased calcification were histologically detected in the deciduous tooth from the patient with complete DiGeorge syndrome. CONCLUSIONS:Common characteristic orofacial and dental findings were noted in the two DiGeorge syndrome cases. Furthermore, histologic study of the deciduous tooth from the boy with complete DiGeorge syndrome suggests that there was some relationship between transient relative hypercalcemia and dentinal hypermineralized streaking of the tooth. 10.1067/moe.2000.103884
    Oral manifestation associated with multiple pituitary hormone deficiency and ectopic neurohypophysis. Scaramucci T,Guglielmi C A B,Fonoff R D,Zardetto C G D The Journal of clinical pediatric dentistry Multiple pituitary hormone deficiency (MPHD) is the diminished secretion of all the hormones produced in the anterior lobe of the pituitary gland. The oral manifestation of this condition includes delayed eruption and prolonged retention of primary teeth, delayed formation and eruption of permanent teeth, delay in development and growth of the jaws, tendency towards development of deep bite and enamel disturbances. This paper reports the case of an adolescent patient with MPHD. Clinical examination revealed partial ankylosis and prolonged retention ofprimary second molars, primary maxillary canines and deep bite. Dental treatment included extraction of all molars with prolonged retention preceded by the necessary medical care with clinical and radiographic follow-up afterwards. The patient was also referred to an orthodontist for orthodontic treatment. Patients' medical condition should always be investigated by clinicians when faced with cases of delayed tooth eruption and bone development. 10.17796/jcpd.35.4.u66627v5m0212547
    Masculinization of the eruption pattern of permanent mandibular canines in opposite sex twin girls. Heikkinen Tuomo,Harila Virpi,Tapanainen Juha S,Alvesalo Lassi American journal of physical anthropology The aim of this study is to explore the effect of prenatal androgenization on the clinical eruption of permanent teeth expressing dimorphism and bimaturism. The eruption curves of permanent teeth (except third molars), including those that make up the canine complex (permanent canines, lower first premolars), are compared among opposite sex twins (OS twins) relative to single-born boys and girls. The comparisons are made with regard to three phases of eruption (pierced mucosa, half- erupted, and completely erupted) from a cross-sectional sample of dental casts, using Kaplan-Meier survival and Cox regression analyzes. The casts were collected from 2159 school children from the US Collaborative Perinatal Project, including 39 pairs of OS-twins, of which 12 pairs (30.8%) were Euro-Americans and 27 pairs (69.2%) were of African-American ancestry. The eruption patterns of the incisors, upper first molars, and lower canines were found to be significantly masculinized (delayed) among OS twin girls. The differences in most other teeth were either not significant, or the number of observations of active eruption phases were too few, such as in the upper first molars and incisors, to yield strong evidence and meaningful results. The masculinization of the tooth eruption pattern in OS twin girls is intriguing because of the lower canine responses during puberty, as well as canine primordial formation during early fetal androgenization of their co-twin during the 8th to 14th gestational weeks. The present results offer a challenge for future research exploring tooth eruption mechanisms, and may also highlight some cases of delayed or ectopic canines, which are biased toward females. 10.1002/ajpa.22298
    Growth hormone receptor and insulin-like growth factor-I immunoreactivity in osteoclast-like cells during tooth eruption in the toothless (osteopetrotic) rat following treatment with colony-stimulating factor-1. Symons Anne L,Weerakoon Arosha,Marks Sandy C Critical reviews in eukaryotic gene expression In the toothless (tl/tl) osteopetrotic rat, teeth form but fail to erupt. Treatment of tl/tl rats with colony-stimulating factor-1 (CSF-1) activates bone resorption by osteoclasts, permits tooth eruption, and up-regulates the immunoreactivity of bone marrow mononuclear cells to growth hormone receptor (GHr) and insulin-like growth factor (IGF)-I. This study examined the distribution of tartrate-resistant acid phosphatase (TRAP) and immunoreactivity for GHr and IGF-I in osteoclast-like cells located on the alveolar bone margin, adjacent to the lower first molar crown, in 14-day-old normal and tl/tl rats, following treatment with CSF-1. Osteoclast-like cells demonstrated a positive reaction for TRAP, GHr, and IGF-I in all groups. However, in tl/tl tissue, osteoclast-like cells were generally negative for GHr. There was no significant difference in the total number of TRAP-, GHr-, and IGF-I-positive osteoclast-like cells on the adjacent bone margin in normal, normal treated with CSF-1, and tl/tl rats. CSF-1 treatment of the tl/tl rat significantly increased the total number of osteoclast-like cells, which were positive for TRAP (p < 0.001), GHr (p < 0.05) and IGF-I (p < 0.01). 10.1615/critreveukaryotgeneexpr.v13.i24.120
    Localization of epidermal growth factor receptors in cells of the enamel organ of the rat incisor. Martineau-Doizé B,Warshawsky H,Dickson K,Lai W H,Bergeron J J Developmental biology Epidermal growth factor (EGF) is a peptide shown to effect precocious incisor tooth eruption in rat pups. Binding sites for EGF were visualized in the continuously erupting adult rat incisor by light and electron microscope radioautography after in vivo injection of 125I-EGF. These binding sites represented EGF receptors because of (i) competition between 125I-EGF binding at 2 min after injection and a coinjected excess of unlabeled EGF; (ii) the receptor-mediated endocytosis of 125I-EGF at 15 and 30 min after injection; and (iii) the demonstration of EGF receptor kinase activation in vivo. The stem and the mitotic cells in the epithelial odontogenic organ at the growing end of the tooth develop into two nondividing layers of the enamel organ: (i) ameloblasts which secrete enamel and are subsequently involved in the enamel maturation process, and (ii) papillary layer cells situated between the blood supply and the ameloblasts. Although few EGF receptors were present at the mitotic end, receptor density was highest at the mature end of the enamel organ. High levels of 125I-EGF binding were found on papillary layer cells and ruffle-ended, but not smooth-ended, ameloblasts. This implies a cyclical exteriorization and internalization of receptors during modulations between the two cell types. These data suggest that the EGF receptor mediates a major function of the enamel organ in the formation of enamel. 10.1016/0012-1606(91)90276-9
    SOME DENTAL ASPECTS OF ENDOCRINE DISEASES. LEVIN H L Oral surgery, oral medicine, and oral pathology 10.1016/0030-4220(65)90006-x
    Abnormalities of GH secretion in a young girl with Floating-Harbor syndrome. Cannavò S,Bartolone L,Lapa D,Venturino M,Almoto B,Violi A,Trimarchi F Journal of endocrinological investigation We present a 9.1-year-old girl of Calabrian (Italy) ancestry, with clinical features (cranio-facial dysmorphism, short stature with delayed bone age and speech delay) suggesting the diagnosis of Floating-Harbor syndrome (FHS). Physical examination showed: height 113.9 cm (-2.9 SD), with a parent's target of 156.2 cm (+1.0 SD), weight 20.7 kg, BMI 16.0 (-0.04 SD), and many phenotypic abnormalities: long eyelashes, large bulbous nose with broad nasal bridge, short philtrum, moderately broad mouth, tooth folding and malocclusion, posteriorly rotated ears, low posterior hair line, short neck, clinodactyly of the 5th finger and hyperextensible finger joints. Diffused hyperpigmentation and hypertrichosis with sporadic pubic terminal hairs, but neither clitoromegaly nor other signs of hyperandrogenism and/or precocious puberty, were observed (T1, P1). Carpal bone evaluation showed a delayed bone age (TW2: 5-5/10, - 3.6 yr) and the statural age/bone age ratio was 1.1. Other dysmorphic syndromes were excluded on the basis of clinical evidence, also evaluated by a computer-assisted search (P.O.S.S.U.M. version 3.5, 1992). Analysis of chromosome 22 by the FISH method, using specific probes Cos29 and Tuple1, excluded microdeletions in the region 22q11.2, typical of Velo-cardio-facial syndrome. In this case, we report the impairment of serum GH responsiveness (GH baseline values: 0.2-1.9 ng/ml) to the administration of oral 150 microg clonidine [peak 4.7 ng/ml, normal values (nv)>10 ng/ml] and oral 4 mg dexamethasone (8.1 ng/ml, nv>10 ng/ml). Moreover, the evaluation of spontaneous 24-h GH secretion (Carmeda AB, Stockholm, Sweden) showed low mean GH levels (1.75 ng/ml, nv>3.0 ng/ml), with a maximum sleep-related peak of 2.8 ng/ml. Serum IGF-1 values were in the low-normal range (80-176 ng/ml, nv 133-626 ng/ml). While in FHS the cranio-facial features minimize with advancement of age, the impairment of growth velocity is permanent and results in severe dwarfism. In our case, treatment with recombinant GH (0.10 U/kg/day), administered by a needle-free device, induced a dramatic increase of growth velocity, increasing the height from -2.8 to -1.9 SD after 18 months, thus indirectly confirming a role of GH deficiency in the pathogenesis of FHS dwarfism. 10.1007/BF03343962
    An autoradiographic study on the effect of epidermal growth factor on cell proliferation in erupting mouse incisors. Rihtniemi L,Thesleff I Archives of oral biology Epidermal growth factor (EGF) is a small polypeptide that induces precocious eyelid opening and incisor eruption in newborn mice; it stimulates cell proliferation in various cell types in vitro and in vivo. EGF was injected twice daily into newborn mice (0.4 microgram/g) and tritiated thymidine was injected subcutaneously 6 h before killing the mice. Longitudinal sections of the lower incisors showed significantly more thymidine-labelled mitoses in the pre-odontoblast and pre-ameloblast layers at the basal ends of incisors in EGF-treated mice than in control mice. Although these results indicate that the EGF-induced precocious tooth emergence is associated with a stimulation of cell proliferation in the root sheath, this tissue may not be the target for the actions of EGF. Earlier studies have shown that root growth is not a factor in the generation of the eruptive force and, as neither the pre-ameloblasts nor pre-odontoblasts express EGF-receptors, the stimulation of cell proliferation in the root-sheath region appears to be a result and not a cause of accelerated tooth eruption, i.e. the increase in root growth may meet the need to maintain the tooth positionally during the accelerated eruptive process. 10.1016/0003-9969(87)90098-7
    [Evaluation of total nitrogen in the incisors of newborn rats subjected to the action of anabolic steroids]. Porzio P A Minerva stomatologica
    Effect of estrone on tooth buds and bones in growing dogs. BAUER W H The Journal of the American College of Dentists
    Dental maturity in children of short stature--a two-year longitudinal study of growth hormone substitution. Krekmanova L,Carlstedt-Duke J,Marcus C,Dahllöf G Acta odontologica Scandinavica The aim of this investigation was to present the 2-year follow-up results of a longitudinal study examining the influence of growth hormone (GH) substitution on dental maturity in healthy children of short stature (height <2 SD). At baseline, the children were divided into a GH-deficient group and a GH non-deficient group, and comparisons were made with healthy controls (height between -2 SD and 2 SD) and between the short stature groups. The GH-substituted group included 24 children (8 F, 16 M) with a mean chronological age of 12.20 +/- 2.40 years, whereas the GH non-substituted group included 19 children (5 F, 14 M) with a mean chronological age of 11.00 +/- 2.40 years. The corresponding age- and sex-matched control groups constituted 48 and 36 children, respectively. The mean dental age in the GH-substituted group was 11.60 +/- 2.70 years, compared to their healthy controls 12.40 +/- 2.60 years (P< 0.05). The dental age for the GH non-substituted children was 10.20 +/- 2.60 years compared to their controls 11.90 +/- 2.60 years (P< 0.001). GH-substituted children show an acceleration in their dental maturity in contrast to controls, whereas in non-substituted children the acceleration is less pronounced.
    The mandibles of castrated male rhesus macaques (Macaca mulatta): The effects of orchidectomy on bone and teeth. Wang Qian,Kessler Matthew J,Kensler Terry B,Dechow Paul C American journal of physical anthropology OBJECTIVES:The objectives of this study were to evaluate the long-term effects of orchidectomy and low testosterone on the craniofaciodental development and maintenance of skeletal and oral health in rhesus macaques. MATERIALS AND METHODS:Mandibles of four castrated and intact age-matched male rhesus monkeys (Macaca mulatta) from Cayo Santiago were compared for mandibular morphology and teeth, abnormalities, pathology, and cortical bone thickness and density using a digital sliding caliper and analysis of three-dimensional X-ray images. RESULTS:Although all four castrates were generally comparable to intact males in overall mandible and teeth size, there were some significant differences. In the castrates, (1) the distance between the two rami was narrower than in intact males leading to a relatively narrower and longer face; (2) both the mandibular body and ramus had thinner cortical bone leading to less total bone mass; and (3) the canines and molar teeth were slender with lower and less robust tooth cusps. In addition, the alveolar bone of two geriatric castrates was greatly receded with signs of periodontitis more severe than in intact aged males. Old castrates also had severe temporomandibular joint osteoarthritis. DISCUSSION:The findings suggest the importance of testosterone in craniofaciodental development, and maintenance of skeletal and oral health in male macaques. These results suggest that dental health professionals might want to include in their medical history questionnaires whether or not male patients have taken hormone (testosterone) replacement therapy. 10.1002/ajpa.22833
    [Endocrine factors in dental development]. Job J C,Mugnier A Revue francaise d'odonto-stomatologie
    [Preliminary data to research on growth hormone influences involving the development of tooth germs (from subcapsular renal transplants in rats)]. Berard R Bulletin de Groupement europeen pour la recher che scientifique en stomatologie & odontologie
    Intrauterine hormone effects on tooth dimensions. Ribeiro D C,Brook A H,Hughes T E,Sampson W J,Townsend G C Journal of dental research The human dentition is a complex adaptive system that is influenced by genetic, epigenetic, and environmental factors. Within this system, is sexual dimorphism related to the growth promotion of the Y chromosome, or to hormonal influences, or both? This study is the first to investigate both primary and permanent tooth sizes in females from opposite-sex dizygotic (DZOS) twin pairs compared with females from dizygotic same-sex (DZSS) and monozygotic (MZ) twin pairs to indicate the influence of intrauterine male hormone, including the initial testosterone surge, on dental development. Serial dental models of the primary, mixed, and permanent dentitions of 134 females from DZOS, DZSS, and MZ twins were examined. Mesiodistal, buccolingual, crown height, and intercuspal dimensions of all primary teeth and selected permanent teeth were determined by image analysis. Univariate and multivariate analyses showed statistically significantly larger crown size in DZOS females in both dentitions, with the crown height dimensions displaying the greatest increase in size. These findings strongly support the Twin Testosterone Transfer (TTT) hypothesis. We propose that the growth-promoting effects of the Y chromosome and intrauterine male hormone levels influence different tooth dimensions and contribute differentially to the sexual dimorphism of human teeth. 10.1177/0022034513484934
    Expression status of mRNA for sex hormone receptors in human dental pulp cells and the response to sex hormones in the cells. Inaba Tomohiro,Kobayashi Tomoko,Tsutsui Takeo W,Ogawa Masaaki,Uchida Minoru,Tsutsui Takeki Archives of oral biology OBJECTIVES:Sex hormone receptors are reported to be present in human dental pulp (HDP) cells. The purpose of this study was to examine the biological significance of oestrogen and androgen receptors (ER and AR, respectively) in HDP cells. DESIGN:We isolated HDP cells expressing ER- and AR-mRNAs and investigated the expression status of the receptors and the response to sex hormones in the cells. RESULTS:HDP cells expressing ER- and/or AR-mRNAs had the ability to form alizarin red S-positive nodules in which calcium and phosphorus were deposited in vitro and to differentiate into odontoblasts-like cells and dentine-like tissue in vivo. Individual clones isolated from HDP cells exhibited a different expression pattern of mRNA for ER and AR. Some clones expressed ERα- and/or ERβ-mRNAs and the others coexpressed ER- and AR-mRNAs. Using the Ingenuity software, we found that 17β-estradiol (E2) and dihydrotestosterone (DHT) could act directly on HDP cells through ER-or androgen signalling-mediated mechanisms. E2 or DHT stimulated the mRNA expression for genes related to odontogenesis of dentine-containing teeth and odontoblast differentiation, suggesting that ER and AR in HDP cells may be involved in dentinogenesis. CONCLUSIONS:Our findings provide new insights into the biological significance of sex hormone receptors in HDP cells. 10.1016/j.archoralbio.2013.02.001
    Does exogenous female sex hormone administration affect the rate of tooth movement and root resorption? A systematic review of animal studies. Kaklamanos Eleftherios G,Makrygiannakis Miltiadis A,Athanasiou Athanasios E PloS one BACKGROUND:The long-term use of contraceptive methods that contain estrogens, progestogens or combinations of the above among women aged 15 to 49 years is extensive. Both estrogens and progestogens affect bone metabolism. OBJECTIVE:To systematically investigate and appraise the quality of the available evidence from animal studies regarding the impact of exogenous administration of female sex hormones on the rate of orthodontic tooth movement and root resorption. SEARCH METHODS:Search without restriction in seven databases (including grey literature) and hand searching were performed until May 2021. SELECTION CRITERIA:We looked for controlled animal studies investigating the effect from exogenous administration of formulations containing female sex hormones on the rate of orthodontic tooth movement and root resorption. DATA COLLECTION AND ANALYSIS:After study retrieval and selection, relevant data was extracted, and the risk of bias was assessed using the SYRCLE's Risk of Bias Tool. The quality of available evidence was assessed with the Grades of Recommendation, Assessment, Development, and Evaluation. RESULTS:Three studies were identified, all being at unclear risk of bias. Overall, administration of progesterone and the combinations of estradiol with norgestrel and desogestrel were shown to significantly decrease the rate of orthodontic tooth movement when given for longer periods (>3 weeks). Inconsistent information was detected for shorter periods of consumption. Estradiol, with desogestrel use, resulted in less root resorption. The quality of the available evidence was considered to be low. CONCLUSIONS:Exogenous administration of female sex hormones may decelerate in the long term the rate of tooth movement and decrease orthodontically induced root resorption in animals. Until more information becomes available, an orthodontist should be able to identify a patient consuming such substances and understand the potential clinical implications and adverse effects that may arise. REGISTRATION:PROSPERO: CRD42017078208; https://clinicaltrials.gov/. 10.1371/journal.pone.0257778
    Effects of estrogen deficiency during puberty on maxillary and mandibular growth and associated gene expression - an μCT study on rats. Küchler Erika Calvano,de Lara Rafaela Mariana,Omori Marjorie Ayumi,Marañón-Vásquez Guido,Baratto-Filho Flares,Nelson-Filho Paulo,Stuani Maria Bernadete Sasso,Blanck-Lubarsch Moritz,Schroeder Agnes,Proff Peter,Kirschneck Christian Head & face medicine BACKGROUND:Estrogen is a well-known and important hormone involved in skeletal homeostasis, which regulates genes involved in bone biology. Some studies support that estrogen is important for craniofacial growth and development. Therefore this in vivo animal study aimed to investigate, whether and in which way low estrogen levels in the prepubertal period affect craniofacial development in the postpubertal stage and to quantify the gene expression of RANK, RANKL and OPG in cranial growth sites in ovariectomized estrogen-deficient rats during puberty. METHODS:Control (sham-operated, n = 18) and ovariectomy (OVX, n = 18) surgeries were performed on 21-days-old female Wistar rats. Animals euthanized at an age of 45 days (pubertal stage) were used for gene expression analyses (n = 6 per group) and immunohistochemistry of RANK, RANKL and OPG. Animals euthanized at 63 days of age (post-pubertal stage) were used for craniofacial two-dimensional and three-dimensional craniofacial measurements using μCT imaging (n = 12 per group). RESULTS:In the μCT analysis of the mandible and maxilla many statistically significant differences between sham-operated and OVX groups were observed, such as increased maxillary and mandibular bone length in OVX animals (p < 0.05). Condylar volume was also significantly different between groups (p < 0.05). The sham-operated group showed a higher level of RANK expression in the midpalatal suture (p = 0.036) and the RANKL:OPG ratio levels were higher in the OVX group (p = 0.015). CONCLUSIONS:Our results suggest that estrogen deficiency during the prepubertal period is associated with alterations in the maxillary and mandibular bone length and condylar growth. 10.1186/s13005-021-00265-3
    Epidermal growth factor-induced precocious incisor eruption is associated with decreased tooth size. Rhodes J A,Fitzgibbon D H,Macchiarulo P A,Murphy R A Developmental biology Epidermal growth factor (EGF) causes precocious eruption of incisors in vivo and is mitogenic for tooth-derived cells in vitro. These two observations lead to the hypothesis that the EGF-induced precocious eruption is the result of an increase in the size of the incisor. To test this hypothesis, neonatal mice were injected daily with various doses of EGF and, seven days after birth, were perfused with fixative. EGF causes a retardation of overall growth (as measured by body weight) and a dose-dependent thickening of the epidermis. The incisors were examined in midsagittal histological sections and in X-ray microradiographs. Contrary to our expectations, EGF causes a dose-dependent decrease in the size of the incisors. This result suggests that the stimulation of the growth of odontogenic cells seen in tissue culture is not part of the physiological response to EGF in vivo and that EGF-induced precocious eruption of incisors is not due to an increase in the growth rate of the tooth. 10.1016/0012-1606(87)90156-4