Age effect on orthodontic tooth movement rate and the composition of gingival crevicular fluid : A literature review.
Journal of orofacial orthopedics = Fortschritte der Kieferorthopadie : Organ/official journal Deutsche Gesellschaft fur Kieferorthopadie
PURPOSE:To evaluate and form a comprehensive understanding of the effect of patient age on bone remodeling and consequently on the rate of orthodontic tooth movement (OTM). METHODS:A systematic search in PubMed and Embase from 1990 to December 2017 was performed and completed by a hand search. Prospective clinical trials which investigated the rate of OTM and/or studies assessing age-related changes in the composition of gingival crevicular fluid (GCF) in older compared to younger study groups were included. Study selection, data extraction and risk of bias were assessed by two authors. RESULTS:Eight studies fulfilled the inclusion criteria. Among them, four evaluated the rate of OTM and six investigated mediators in the GCF (prostaglandin E, interleukin [IL]-1β, IL‑6, IL‑1 receptor antagonist, receptor activator of nuclear factor kappa‑Β ligand, osteoprotegerin, granulocyte-macrophage colony-stimulating factor, pentraxin 3). Patient age ranged between 16 and 43 years for older and <16 years for younger groups. In most of the studies, the younger patients showed faster OTM in the first phase of treatment and more pronounced cytokine levels. Older patients had a delayed reaction to orthodontic forces. CONCLUSION:The small number of included studies and large heterogeneity in study design give limited clinical evidence that the older patients are less responsive to orthodontic force in comparison to younger patients. The initial cellular response to orthodontic force is expected to be delayed in older patients. Control intervals during orthodontic treatment should be adjusted to the individual's treatment response.
10.1007/s00056-019-00206-5
Plexin-B2 Mediates Orthodontic Tension-Induced Osteogenesis via the RhoA/F-Actin/YAP Pathway.
Journal of periodontal research
AIMS:This study aims to investigate the role of Plexin-B2 in tension-induced osteogenesis of periodontal ligament stem cells (PDLSCs) and its biomechanical mechanism. METHODS:In vitro, cyclic tension simulated orthodontic forces to assess Plexin-B2 expression in PDLSCs. We then knocked out Plexin-B2 using lentivirus to explore its role in tension-induced osteogenesis. In vivo, we used nickel-titanium springs to establish orthodontic tooth movement (OTM) models in mice. Local periodontal Plexin-B2 expression was knocked down using adeno-associated viruses (AAVs) to study its influence on new bone formation under mechanical tension in OTM models. Molecular mechanisms were elucidated by manipulating Plexin-B2 and RhoA expression, assessing related proteins, and observing F-actin and Yes-associated protein (YAP) through immunofluorescence. RESULTS:Plexin-B2 expression in PDLSCs increased under cyclic tension. Decrease of Plexin-B2 reduced the expression of osteogenic protein in PDLSCs and negatively affected new bone formation during OTM. RhoA expression and phosphorylation of ROCK2/LIMK2/Cofilin decreased in Plexin-B2 knockout PDLSCs but were reversed by RhoA overexpression. The level of F-actin decreased in Plexin-B2 knockout PDLSCs but increased after RhoA rescue. Nuclear YAP was reduced in Plexin-B2 knockout PDLSCs but increased after RhoA overexpression. CONCLUSIONS:Plexin-B2 is involved in tension-induced osteogenesis. Mechanistically, the RhoA signaling pathway, the F-actin arrangement, and the nuclear translocation of YAP are involved in the mechanotransduction of Plexin-B2.
10.1111/jre.13358
AGEs impair osteogenesis in orthodontic force-induced periodontal ligament stem cells through the KDM6B/Wnt self-reinforcing loop.
Stem cell research & therapy
BACKGROUND:Diabetes, occasionally diagnosed in orthodontic patients, can impede orthodontic tooth movement (OTM) by accumulating advanced glycation end products (AGEs) in the periodontium. This accumulation impairs the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) due to alterations in the force-loaded microenvironment, yet the underlying mechanisms remain elusive. METHODS:Bioinformatics analysis of GSE112122 identified alterations in the mechanical regulation of histone methylation enzyme Lysine Demethylase 6B (KDM6B). OTM models were established in healthy and Nicotinamide/ Streptozotocin-induced type II diabetic rats. The impact of AGEs on mechanically induced osteogenesis and its correlation with KDM6B were evaluated by assessing the therapeutic effects of periodontal ligament injections of the AGEs/RAGE inhibitor FPS-ZM1. To investigate transcriptomic changes, we extracted human PDLSCs, which were subjected to RNA sequencing following the overexpression of KDM6B. Experimental validation further identified potential self-reinforcing loops and their associated antioxidative mechanisms. RESULTS:Mechanical forces upregulated KDM6B expression and function in PDLSCs, modulating extensive downstream osteogenesis-related transcriptional changes. Experiments with AGEs-treated and FPS-ZM1-treated samples demonstrated that AGEs impaired osteogenesis by compromising KDM6B mechanical responsiveness. A positive feedback loop between KDM6B and Wnt pathways was identified, inhibited by AGEs. This loop regulated superoxide dismutase 2 (SOD2), facilitating antioxidative stress and preventing stem cell ageing. CONCLUSIONS:This study elucidates a novel mechanism by which AGEs influence the osteogenic process and antioxidative capacity of PDLSCs through the KDM6B/Wnt self-reinforcing loop under orthodontic force. Targeting the AGE/RAGE pathway or enhancing KDM6B may enhance orthodontic treatments for diabetic patients.
10.1186/s13287-024-04058-8
Calcium phosphate nanoclusters modify periodontium remodeling and minimize orthodontic relapse.
Biomaterials
Orthodontic relapse is one of the most prevalent concerns of orthodontic therapy. Relapse results in patients' teeth reverting towards their pretreatment positions, which increases the susceptibility to functional problems, dental disease, and substantially increases the financial burden for retreatment. This phenomenon is thought to be induced by rapid remodeling of the periodontal ligament (PDL) in the early stages and poor bone quality in the later stages. Current therapies including fixed or removable retainers and fiberotomies have limitations with patient compliance and invasiveness. Approaches using biocompatible biomaterials, such as calcium phosphate polymer-induced liquid precursors (PILP), are an ideal translational approach for minimizing orthodontic relapse. Here, post-orthodontic relapse is reduced after a single injection of high concentration PILP (HC-PILP) nanoclusters by altering PDL remodeling in the early stage of relapse and improving trabecular bone quality in the later stage. HC-PILP nanoclusters are achieved by using high molecular weight poly aspartic acid (PASP, 14 kDa) and poly acrylic acid (PAA, 450 kDa), which resulted in a stable solution of high calcium and phosphate concentrations without premature precipitation. In vitro results show that HC-PILP nanoclusters prevented collagen type-I mineralization, which is essential for the tooth-PDL-bone interphase. In vivo experiments show that the HC-PILP nanoclusters minimize relapse and improve the trabecular bone quality in the late stages of relapse. Interestingly, HC-PILP nanoclusters also altered the remodeling of the PDL collagen during the early stages of relapse. Further in vitro experiments showed that HC-PILP nanoclusters alter the fibrillogenesis of collagen type-I by impacting the protein secondary structure and forming aggregates. These findings propose a new approach for treating orthodontic relapse and provide additional insight into the PILP nanocluster's structure and properties on collagenous structure repair.
10.1016/j.biomaterials.2024.122965
Ubiquitin C-terminal hydrolase L1 activation in periodontal ligament cells mediates orthodontic tooth movement via the MAPK signaling pathway.
Connective tissue research
PURPOSE:Periodontal ligament cells (PDLCs) play a significant role in orthodontic force induced bone remodeling. However, the molecular mechanisms by which PDLCs respond to mechanical stimuli and influence osteoclastic activities remain unclear. This study aims to investigate the role of UCHL1, a key deubiquitinating enzyme involved in protein degradation and cellular responses, in force-treated PDLCs during orthodontic tooth movement (OTM). MATERIALS AND METHODS:In this study, we conducted and experiments using human PDLCs and a rat model of OTM. Mechanical stress was applied to PDLCs, and UCHL1 expression was analyzed through quantitative real-time polymerase chain reaction (qPCR), Western blot, and immunofluorescence staining. UCHL1 knockdown was achieved using siRNA, and its effects on osteoclast differentiation were assessed. The role of the MAPK/ERK pathway was investigated using the MEK-specific inhibitor U0126. An animal model of OTM was established, and the impact of UCHL1 inhibitor-LDN57444 on OTM and osteoclastic activity was evaluated through micro-CT analysis, histological staining, and immunohistochemistry. RESULTS:Mechanical force induced UCHL1 expression in PDLCs during OTM. UCHL1 knockdown downregulated the RANKL/OPG ratio in PDLCs, affecting osteoclast differentiation. LDN57444 inhibited OTM and osteoclastic activity. UCHL1 activation correlated with ERK1/2 phosphorylation in force-treated PDLCs. CONCLUSIONS:Mechanical force mediated UCHL1 activation in PDLCs promotes osteoclast differentiation via the ERK1/2 signaling pathway during OTM.
10.1080/03008207.2024.2395998
Semaphorin 3A protects against alveolar bone loss during orthodontic tooth movement in mice with periodontitis.
Journal of periodontal research
OBJECTIVE:This study investigated the effect of local semaphorin 3A (Sema3A) administration on alveolar bone loss during OTM in a mouse model of periodontitis. BACKGROUND:Orthodontic tooth movement (OTM) for patients with periodontal disease is known to increase the risk of exacerbating alveolar bone loss due to inflammation of the periodontal tissue. However, its mechanism of action and prevention remains unclear. METHODS:Mice (male 7-8 weeks old, C57BL/6J, n = 12) were divided into six groups: untreated group (control), without OTM and recovered from induced periodontitis (RP), with OTM and administered PBS or Sema3A to the gingiva after induced periodontitis (VehPO, SemaPO), with OTM and administered PBS or Sema3A to the gingiva without periodontitis induction (VehNO, SemaNO). Samples were collected on 14 days, and bone loss, histological analysis, cytokine production level, and tooth movement were assessed. Cultured human periodontal ligament (hPDL) cells were stimulated with lipopolysaccharide (LPS) and compressive force (CF), and mRNA expression levels of Sema3A and its receptors were analyzed. RESULTS:The bone loss was significantly lower in the SemaPO group than in the VehPO group. The number of TRAP-positive cells in the SemaPO group was significantly lower than that in the VehPO group and was at the same level as that in the control group. The receptor activator of nuclear factor (NF)-kB-ligand/osteoprotegerin (RANKL/OPG) ratio and the levels of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, IL-17, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ, in the gingival tissues were significantly lower in the SemaPO group than in the VehPO group. Additionally, Sema3A mRNA expression in hPDL cells was significantly decreased by co-stimulation with LPS and CF compared with that in the control group. Finally, the distance moved (dist.) and the mesial tipping angle (θ) was significantly smaller in the SemaPO group than in the VehPO group and was not significantly different from that of VehNO. CONCLUSION:Pathological alveolar bone loss exacerbated by OTM in periodontitis might be prevented by local administration of Sema3A without inhibiting OTM.
10.1111/jre.13038