Distinct tooth regeneration systems deploy a conserved battery of genes.
Square Tyler A,Sundaram Shivani,Mackey Emma J,Miller Craig T
BACKGROUND:Vertebrate teeth exhibit a wide range of regenerative systems. Many species, including most mammals, reptiles, and amphibians, form replacement teeth at a histologically distinct location called the successional dental lamina, while other species do not employ such a system. Notably, a 'lamina-less' tooth replacement condition is found in a paraphyletic array of ray-finned fishes, such as stickleback, trout, cod, medaka, and bichir. Furthermore, the position, renewal potential, and latency times appear to vary drastically across different vertebrate tooth regeneration systems. The progenitor cells underlying tooth regeneration thus present highly divergent arrangements and potentials. Given the spectrum of regeneration systems present in vertebrates, it is unclear if morphologically divergent tooth regeneration systems deploy an overlapping battery of genes in their naïve dental tissues. RESULTS:In the present work, we aimed to determine whether or not tooth progenitor epithelia could be composed of a conserved cell type between vertebrate dentitions with divergent regeneration systems. To address this question, we compared the pharyngeal tooth regeneration processes in two ray-finned fishes: zebrafish (Danio rerio) and threespine stickleback (Gasterosteus aculeatus). These two teleost species diverged approximately 250 million years ago and demonstrate some stark differences in dental morphology and regeneration. Here, we find that the naïve successional dental lamina in zebrafish expresses a battery of nine genes (bmpr1aa, bmp6, cd34, gli1, igfbp5a, lgr4, lgr6, nfatc1, and pitx2), while active Wnt signaling and Lef1 expression occur during early morphogenesis stages of tooth development. We also find that, despite the absence of a histologically distinct successional dental lamina in stickleback tooth fields, the same battery of nine genes (Bmpr1a, Bmp6, CD34, Gli1, Igfbp5a, Lgr4, Lgr6, Nfatc1, and Pitx2) are expressed in the basalmost endodermal cell layer, which is the region most closely associated with replacement tooth germs. Like zebrafish, stickleback replacement tooth germs additionally express Lef1 and exhibit active Wnt signaling. Thus, two fish systems that either have an organized successional dental lamina (zebrafish) or lack a morphologically distinct successional dental lamina (sticklebacks) deploy similar genetic programs during tooth regeneration. CONCLUSIONS:We propose that the expression domains described here delineate a highly conserved "successional dental epithelium" (SDE). Furthermore, a set of orthologous genes is known to mark hair follicle epithelial stem cells in mice, suggesting that regenerative systems in other epithelial appendages may utilize a related epithelial progenitor cell type, despite the highly derived nature of the resulting functional organs.
The Epigenetic Regulation in Tooth Development and Regeneration.
Lin Yao,Zheng Liwei,Fan Li,Kuang Wei,Guo Rui,Lin Jiong,Wu Jiahua,Tan Jiali
Current stem cell research & therapy
BACKGROUND:Tooth loss occurs with age and significantly impacts the quality of elderly's life both physically and psychologically. It has been well known that odontogenesis is a complicated process with sequential and reciprocal interactions between epithelial and mesenchymal tissues and different types of dental tissue-derived stem cells involve in it. However, only a small portion of the intricate mechanisms has been defined nowadays. Among them, epigenetics has become an increasingly important mechanism for tooth development and regeneration. OBJECTIVE:This review aims at illustrating the function of epigenetic regulation in odontogenesis, which plays an important role in dental tissue-derived stem cell self-renewal and differentiation nowadays and would be a new strategy for tooth regeneration. RESULTS:In this review, we introduced the natural process of tooth development and the functions of stem cells involved in. Furthermore, we summarized the current knowledge on epigenetic regulation including DNA methylation, histone modification, and non-coding RNAs during odontogenesis, providing the theoretical basis for tooth regeneration. CONCLUSION:Along with a deeper understanding of odontogenesis, the epigenetic mechanism involved in has become increasingly important. Therefore, it's necessary to further study the functions of epigenetic regulation in tooth development and regeneration, which may make tooth regeneration a reality in the future.
Epigenetics in Odontogenesis and its Influences.
Li Chuwen,Cui Yujia,Zhou Changchun,Sun Jianxun,Zhou Xuedong
Current stem cell research & therapy
BACKGROUND:Odontogenesis is fundamentally controlled by the genome. However, epigenetic factors have indispensable effects during odontogenesis. Previous studies have shown that exogenous factors, such as the environment, that cause hypomethylation and hypermethylation in DNA may lead to dental differences in monozygotic twin pairs. In addition, abnormalities in epigenetic regulation could induce disruptions in odontogenesis, thereby causing tooth malformation or agenesis. OBJECTIVE:This review overviews the epigenetic mechanisms involved in odontogenesis with the aim of establishing a fundamental vision of tooth development, which might be useful in further research in odontogenesis and therapy for dental diseases. RESULTS:We summarized articles about epigenetics in odontogenesis. Here, we present concrete epigenetic regulation mechanisms in odontogenesis that have been reported previously, following the order of microRNA, DNA methylation and histone modification. CONCLUSION:Epigenetic factors influence the proliferation, differentiation or apoptosis of cells that play indispensable roles during the process of odontogenesis which have the ability to exquisitely regulate the tooth number, size and shape.
From understanding tooth development to bioengineering of teeth.
European journal of oral sciences
Remarkable breakthroughs in the fields of developmental biology and stem cell biology during the last 15 yr have led to a new level of understanding regarding how teeth develop and how stem cells can be programmed. As a result, the possibilities of growing new teeth and of tooth bioengineering have been explored. Currently, a great deal is known about how signaling molecules and genes regulate tooth development, and modern research using transgenic mouse models has demonstrated that it is possible to induce the formation of new teeth by tinkering with the signaling networks that govern early tooth development. A breakthrough in stem cell biology in 2006 opened up the possibility that a patient's own cells can be programmed to develop into pluripotent stem cells and used for building new tissues and organs. At present, active research in numerous laboratories around the world addresses the question of how to program the stem and progenitor cells to develop into tooth-specific cell types. Taken together, the remarkable progress in developmental and stem cell biology is now feeding hopes of growing new teeth in the dental clinic in the not-too-distant future.
Pulp Vascularization during Tooth Development, Regeneration, and Therapy.
Rombouts C,Giraud T,Jeanneau C,About I
Journal of dental research
The pulp is a highly vascularized tissue situated in an inextensible environment surrounded by rigid dentin walls, with the apical foramina being the only access. The pulp vascular system is not only responsible for nutrient supply and waste removal but also contributes actively to the pulp inflammatory response and subsequent regeneration. This review discusses the underlying mechanisms of pulp vascularization during tooth development, regeneration, and therapeutic procedures, such as tissue engineering and tooth transplantation. Whereas the pulp vascular system is established by vasculogenesis during embryonic development, sprouting angiogenesis is the predominant process during regeneration and therapeutic processes. Hypoxia can be considered a common driving force. Dental pulp cells under hypoxic stress release proangiogenic factors, with vascular endothelial growth factor being one of the most potent. The benefit of exogenous vascular endothelial growth factor application in tissue engineering has been well demonstrated. Interestingly, dental pulp stem cells have an important role in pulp revascularization. Indeed, recent studies show that dental pulp stem cell secretome possesses angiogenic potential that actively contributes to the angiogenic process by guiding endothelial cells and even by differentiating themselves into the endothelial lineage. Although considerable insight has been obtained in the processes underlying pulp vascularization, many questions remain relating to the signaling pathways, timing, and influence of various stress conditions.
Tooth Repair and Regeneration: Potential of Dental Stem Cells.
Zhang Weibo,Yelick Pamela C
Trends in molecular medicine
Tooth defects are an extremely common health condition that affects millions of individuals. Currently used dental repair treatments include fillings for caries, endodontic treatment for pulp necrosis, and dental implants to replace missing teeth, all of which rely on the use of synthetic materials. By contrast, the fields of tissue engineering and regenerative medicine and dentistry (TERMD) use biologically based therapeutic strategies for vital tissue regeneration, and thus have the potential to regenerate living tissues. Methods to create bioengineered replacement teeth benefit from a detailed understanding of the molecular signaling networks regulating natural tooth development. We discuss how key signaling pathways regulating natural tooth development are being exploited for applications in TERMD approaches for vital tooth regeneration.
Hypodontia: An Update on Its Etiology, Classification, and Clinical Management.
Al-Ani Azza Husam,Antoun Joseph Safwat,Thomson William Murray,Merriman Tony Raymond,Farella Mauro
BioMed research international
Hypodontia, or tooth agenesis, is the most prevalent craniofacial malformation in humans. It may occur as part of a recognised genetic syndrome or as a nonsyndromic isolated trait. Excluding third molars, the reported prevalence of hypodontia ranges from 1.6 to 6.9%, depending on the population studied. Most affected individuals lack only one or two teeth, with permanent second premolars and upper lateral incisors the most likely to be missing. Both environmental and genetic factors are involved in the aetiology of hypodontia, with the latter playing a more significant role. Hypodontia individuals often present a significant clinical challenge for orthodontists because, in a number of cases, the treatment time is prolonged and the treatment outcome may be compromised. Hence, the identification of genetic and environmental factors may be particularly useful in the early prediction of this condition and the development of prevention strategies and novel treatments in the future.
Sonic Hedgehog Signaling and Tooth Development.
Hosoya Akihiro,Shalehin Nazmus,Takebe Hiroaki,Shimo Tsuyoshi,Irie Kazuharu
International journal of molecular sciences
Sonic hedgehog (Shh) is a secreted protein with important roles in mammalian embryogenesis. During tooth development, Shh is primarily expressed in the dental epithelium, from initiation to the root formation stages. A number of studies have analyzed the function of Shh signaling at different stages of tooth development and have revealed that Shh signaling regulates the formation of various tooth components, including enamel, dentin, cementum, and other soft tissues. In addition, dental mesenchymal cells positive for Gli1, a downstream transcription factor of Shh signaling, have been found to have stem cell properties, including multipotency and the ability to self-renew. Indeed, Gli1-positive cells in mature teeth appear to contribute to the regeneration of dental pulp and periodontal tissues. In this review, we provide an overview of recent advances related to the role of Shh signaling in tooth development, as well as the contribution of this pathway to tooth homeostasis and regeneration.
Molecular and cellular mechanisms of tooth development, homeostasis and repair.
Yu Tingsheng,Klein Ophir D
Development (Cambridge, England)
The tooth provides an excellent system for deciphering the molecular mechanisms of organogenesis, and has thus been of longstanding interest to developmental and stem cell biologists studying embryonic morphogenesis and adult tissue renewal. In recent years, analyses of molecular signaling networks, together with new insights into cellular heterogeneity, have greatly improved our knowledge of the dynamic epithelial-mesenchymal interactions that take place during tooth development and homeostasis. Here, we review recent progress in the field of mammalian tooth morphogenesis and also discuss the mechanisms regulating stem cell-based dental tissue homeostasis, regeneration and repair. These exciting findings help to lay a foundation that will ultimately enable the application of fundamental research discoveries toward therapies to improve oral health.