Molecular regulatory mechanism of tooth root development

Abstract

Better understanding of tooth root development may hold the key to artificial tooth regeneration, suggest scientists in China and the US. Based on research published during the last decade, Xiao-Feng Huang of Capital Medical University, Beijing, and Yang Chai of the University of Southern California, Los Angeles, reviewed the molecular mechanisms operating during root formation. Following tooth crown formation in the gums, a collection of cells called Hertwig’s epithelial root sheath (HERS) grows around it. HERS triggers the development of dentin and cementum, both vital materials for healthy roots. HERS cells, however, disperse as the root grows. More research is needed to clarify the fate of these cells, as well as the genetic signaling between two types of dental tissue, the epithelium and mesenchyme. Full understanding of these processes could eventually lead to artificially triggered tooth growth in humans.

Keywords

Hertwig’s epithelial root sheath / periodontium / root development / tooth development

References

[1] Brown H. Hypoplasia of the dentition. Am J Orth Oral Surg, 1944, 32(2): 102-103.

[2] Lind V. Short root anomaly. Scand J Dent Res, 1972, 80(2): 85-93.

[3] Xue Y, Wang W, Mao T. Report of two Chinese patients suffering from CLCN7-related osteopetrosis and root dysplasia. J Craniomaxillofac Surg, 2011, 40(5): 416-420.

[4] McKee MD, Nakano Y, Masica DL. Enzyme replacement therapy prevents dental defects in a model of hypophosphatasia. J Dent Res, 2011, 90(4): 470-476.

[5] Qin H, Yang FS. Calcitonin may be a useful therapeutic agent for osteoclastogenesis syndromes involving premature eruption of the tooth. Med Hypotheses, 2008, 70(5): 1048-1050.

[6] Chai Y, Slavkin HC. Prospects for tooth regeneration in the 21st century: a perspective. Microsc Res Tech, 2003, 60(5): 469-479.

[7] Chai Y, Maxson RE Jr. Recent advances in craniofacial morphogenesis. Dev Dyn, 2006, 235(9): 2353-2375.

[8] Lumsden AG. Spatial organization of the epithelium and the role of neural crest cells in the initiation of the mammalian tooth germ. Development, 1988, 103(Suppl): 155-169.

[9] Miletich I, Sharpe PT. Normal and abnormal dental development. Hum Mol Genet, 2003, 12(1): 69-73.

[10] Jernvall J, Thesleff I. Reiterative signaling and patterning during mammalian tooth morphogenesis. Mech Dev, 2000, 92(1): 19-29.

[11] Thesleff I, Sharpe PT. Signalling networks regulating dental development. Mech Dev, 1997, 67(2): 111-123.

[12] Huang XF, Chai Y. TGF-β signaling and tooth development. Chin J Dent Res, 2010, 13(1): 7-13.

[13] Owens PD. Ultrastructure of Hertwig’s epithelial root sheath during early root development in premolar teeth in dogs. Arch Oral Biol, 1978, 23(2): 91-104.

[14] Diekwisch TG. The developmental biology of cementum. Int J Dev Biol, 2001, 45(5/6): 695-706.

[15] Luan X, Ito Y, Diekwisch TG. Evolution and development of Hertwig’s epithelial root sheath. Dev Dyn, 2006, 235(5): 1167-1180.

[16] Aberg T, Wozney J, Thesleff I. Expression patterns of bone morphogenetic proteins (Bmps) in the developing mouse tooth suggest roles in morphogenesis and cell differentiation. Dev Dyn, 1997, 210(4): 383-396.

[17] Steele-Perkins G, Butz KG, Lyons GE. Essential role for NFI-C/CTF transcription-replication factor in tooth root development. Mol Cell Biol, 2003, 23(3): 1075-1084.

[18] Park JC, Herr Y, Kim HJ. Nfic gene disruption inhibits differentiation of odontoblasts responsible for root formation and results in formation of short and abnormal roots in mice. J Periodontol, 2007, 78(9): 1795-1802.

[19] Huang X, Bringas P, Slavkin HC. Fate of HERS during tooth root development. Dev Biol, 2009, 334(1): 22-30.

[20] Huang X, Xu X, Bringas P Jr. Smad4–Shh–Nfic signaling cascade-mediated epithelial–mesenchymal interaction is crucial in regulating tooth root development. J Bone Miner Res, 2010, 25(5): 1167-1178.

[21] Xu L, Tang L, Jin F. The apical region of developing tooth root constitutes a complex and maintains the ability to generate root and periodontium-like tissues. J Periodontal Res, 2009, 44(2): 275-282.

[22] Kazuhisa N, Ritsuko M, Yasumitsu S. The development of a bioengineered organ germ method. Nat Methods, 2007, 4(3): 227-230.

[23] Sonoyama W, Liu Y, Fang D. Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS ONE, 2006, 1: e79.

[24] Brockes JP, Kumar A. Appendage regeneration in adult vertebrates and implications for regenerative medicine. Science, 2005, 310(5756): 1919-1923.

[25] Atala A. Tissue engineering, stem cells and cloning: current concepts and changing trends. Expert Opin Biol Ther, 2005, 5(7): 879-892.

[26] Slavkin HC, Bavetta LA. Odontogenic epithelial–mesenchymal interactions in vitro. . J Dent Res, 1968, 47(5): 779-785.

[27] Huang XF, Zhao YB, Zhang FM. Comparative of gene expression between orthodontic tooth movement and tooth eruption. Oral Dis, 2009, 15(8): 573-579.

[28] Zeichner-David M. Regeneration of periodontal tissues: cementogenesis revisited. Periodontol 2000, 2006, 41: 196-217.

[29] Fang J, Tang L, Liu XH. Changes of the unique odontogenic properties of rat apical bud cells under the developing apical complex microenvironment. Int J Oral Sci, 2009, 1(1): 26-33.

[30] Tenorio D, Cruchley A, Hughes FJ. Immunocytochemical investigation of the rat cementoblast phenotype. J Periodontal Res, 1993, 28(6 Pt 1): 411-419.

[31] Ten Cate AR. A fine structural study of coronal and root dentinogenesis in the mouse. Observations of the so called von Korff fibers and their contribution to mantle dentine. J Anat, 1978, 125(1): 183-197.

[32] Mullen LM, Richards DW, Quaranta V. Evidence that laminin-5 is a component of the tooth surface internal basal lamina, supporting epithelial cell adhesion. J Periodontal Res, 1999, 34(1): 16-24.

[33] Bègue-Kirn C, Smith A, Loriot M. Comparative analysis of TGF betas, BMPs, IGF1, msxs, fibronectin, osteonectin and bone sialoprotein gene expression during normal and in vitro-induced odontoblast differentiation. Int J Dev Biol, 1994, 38(3): 405-420.

[34] Ruch J, Lesot H, Bègue-Kirn C. Odontoblast differentiation. Int J Dev Biol, 1995, 39(1): 51-68.

[35] Unterbrink A, O’Sullivan M, Chen S. TGF beta-1 downregulates DMP-1 and DSPP in odontoblasts. Connect Tissue Res, 2002, 43(2/3): 354-358.

[36] Oka S, Oka K, Xu X. Cell autonomous requirement for TGF-beta signaling during odontoblast differentiation and dentin matrix formation. Mech Dev, 2007, 124(6): 409-415.

[37] Lee DS, Park JT, Kim HM. Nuclear factor I–C is essential for odontogenic cell proliferation and odontoblast differentiation during tooth root development. J Biol Chem, 2009, 284(25): 17293-17303.

[38] Orban B. The epithelial network in the periodontal membrane. J Am Dent Assoc, 1952, 44(6): 632-635.

[39] Slavkin HC, Bringas P, Bessem C. Hertwig’s epithelial root sheath differentiation and initial cementum and bone formation during long-term organ culture of mouse mandibular first molars using serumless, chemically-defined medium. J Periodontal Res, 1988, 23(1): 28-40.

[40] Thomas HF. Root formation. Int J Dev Biol, 1995, 39(1): 231-237.

[41] BarKana I, Narayanan AS, Grosskop A. Cementum attachment protein enriches putative cementoblastic populations on root surfaces in vitro. . J Dent Res, 2000, 79(7): 1482-1488.

[42] McAllister B, Narayanan AS, Miki Y. Isolation of a fibroblast attachment protein from cementum. J Periodontal Res, 1990, 25(1): 99-105.

[43] Palmer RM, Lumsden AG. Development of periodontal ligament and alveolar bone in homografted recombination’s of enamel organs and papillary, pulpal, and follicular mesenchyme in the mouse. Arch Oral Biol, 1987, 32(4): 281-289.

[44] Yu J, McMahon AP, Valerius MT. Recent genetic studies of mouse kidney development. Curr Opin Genet Dev, 2004, 14(5): 550-557.

[45] del Moral PM, Warburton D. Explant culture of mouse embryonic whole lung, isolated epithelium, or mesenchyme under chemically defined conditions as a system to evaluate the molecular mechanism of branching morphogenesis and cellular differentiation. Methods Mol Biol, 2010, 633: 71-79.

[46] Kobayashi H, Kromminga A, Dunlop TW. A role of melatonin in neuroectodermal–mesodermal interactions: the hair follicle synthesizes melatonin and expresses functional melatonin receptors. FASEB J, 2005, 19(12): 1710-1712.

[47] Yang TL, Hsiao YC, Lin SJ. Biomaterial mediated epithelial–mesenchymal interaction of salivary tissue under serum free condition. Biomaterials, 2010, 31(2): 288-295.

[48] Zhao Z, Rivkees SA. Tissue-specific expression of GTPas RalA and RalB during embryogenesis and regulation by epithelial–mesenchymal interaction. Mech Dev, 2000, 97(1/2): 201-204.

[49] Chabanski MB, Gillam DG, Bulman JS. Prevalence of cervical dentine sensitivity in a population of patients referred to a specialist Periodontology Department. J Clin Periodontol, 1996, 23(11): 989-992.

[50] Shimazu Y, Sato K, Aoyagi K. Hertwig’s epithelial cells and multi-root development of molars in mice. J Oral Biosci, 2009, 51(4): 210-221.

[51] Cerri PS, Katchburian E. Apoptosis in the epithelial cells of the rests of Malassez of the periodontium of rat molars. J Periodontal Res, 2005, 40(5): 365-372.

[52] Cerri PS, Freymuller E, Katchburian E. Apoptosis in the early developing periodontium of rat molars. Anat Rec, 2000, 258(2): 136-144.

[53] Kaneko H, Hashimoto S, Enokiya Y. Cell proliferation and death of Hertwig’s epithelial root sheath in the rat. Cell Tissue Res, 1999, 298(1): 95-103.

[54] Wentz FM, Weinmann JP, Schour I. The prevalence, distribution, and morphologic changes of the epithelial remnants in the molar region of the rat. J Dent Res, 1950, 29(2): 637-646.

[55] Sonoyama W, Seo BM, Yamaza T. Human Hertwig’s epithelial root sheath cells play crucial roles in cementum formation. J Dent Res, 2007, 86(7): 594-599.

[56] Zeichner-David M, Oishi K, Su Z. Role of Hertwig’s epithelial root sheath cells in tooth root development. Dev Dyn, 2003, 228(4): 651-663.

[57] Andujar MB, Maglorie H, Hartmann DJ. Early mouse molar root development: cellular changes and distribution of fibronectin, laminin and type-IV collagen. Differentiation, 1985, 30(2): 111-122.

[58] Yamashiro T, Tummers M, Thesleff I. Expression of bone morphogenetic proteins and Msx genes during root formation. J Dent Res, 2003, 82(3): 172-176.

[59] Yamashiro T, Tummers M, Thesleff I. Modulation of epithelial cell fate of the root in vitro. J Dent Res, 2007, 86(11): 1063-1067.

[60] Hammerschmidt M, Brook A, McMahon AP. The world according to hedgehog. Trends Genet, 1997, 13(1): 14-21.

[61] Dassule HR, Lewis P, Bei M. Sonic hedgehog regulates growth and morphogenesis of the tooth. Development, 2000, 127(22): 4775-4785.

[62] Koyama E, Wu CS, Shimo T. Development of stratum intermedium and its role as a Sonic hedgehog-signaling structure during odontogenesis. Dev Dyn, 2001, 222(2): 178-191.

[63] Nakao A, Kajiya H, Fukushima H. PTHrP induces Notch signaling in periodontal ligament cells. J Dent Res, 2009, 88(6): 551-556.

[64] Massague J. How cells read TGF-b signals. Nat Rev Mol Cell Biol, 2000, 1(3): 169-178.

[65] Siegel PM, Massagué J. Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat Rev Cancer, 2003, 3(11): 807-821.

[66] Massagué J, Weis-Garcia F. Serine/threonine kinase receptors: mediators of transforming growth factor beta family signals. Cancer Surv, 1996, 27: 41-64.

[67] Lagna G, Hata A, Hemmati-Brivanlou A. Partnership between DPC4 and Smad proteins in TGF-β signaling pathways. Nature, 1996, 383(6603): 832-836.

[68] Wu R, Zhang Y, Feng X. Heteromeric and homomeric interactions correlate with signaling activity and functional cooperativity of Smad3 and Smad4 (DPC4). Mol Cell Biol, 1997, 17(5): 2521-2528.

[69] Derynck R, Zhang YE. Smad-dependent and Smad-independent pathways in TGF-β family signalling. Nature, 2003, 425(6958): 577-584.

[70] Li JY, Huang XF, Xu X. Smad4-mediated WNT signaling controls the fate of cranial neural crest cells during tooth morphogenesis. Development, 2011, 138(10): 1977-1989.

[71] Smith AJ, Matthews JB, Hall RC. Transforming growth factor-beta1 (TGF-beta1) in dentine matrix. Ligand activation and receptor expression. Eur J Oral Sci, 1998, 106(Suppl 1): 179-184.

[72] Hwang YC, Hwang IN, Oh WM. Influence of TGF-beta1 on the expression of BSP, DSP, TGF-beta1 receptor I and Smad proteins during reparative dentinogenesis. J Mol Histol, 2008, 39(2): 153-160.

[73] Thyagarajan T, Sreenath T, Cho A. Reduced expression of dentin sialophosphoprotein is associated with dysplastic dentin in mice overexpressing transforming growth factor-β1 in teeth. J Biol Chem, 2001, 276(14): 11016-11020.

[74] Gronostajski RM. Role of NFI/CTF gene family in transcription and development. Gene, 2000, 249(1/2): 31-45.

[75] Yokohama TT, Ohshima H, Fujiwara N. Cessation of Fgf10 signaling, resulting in a defective dental epithelial stem cell compartment, leads to the transition from crown to root formation. Development, 2006, 133(7): 1359-1366.

[76] Madan AK, Kramer B. Immunolocalization of fibroblast growth factor-2 (FGF-2) in the developing root and supporting structures of the murine tooth. J Mol Histol, 2005, 36(3): 171-178.

[77] Harada H, Toyono T, Toyoshima K. FGF10 maintains stem cell compartment in developing mouse incisors. Development, 2002, 129(6): 1533-1541.

[78] Sakuraba H, Fujiwara N, Sasaki-Oikawa A. Hepatocyte growth factor stimulates root growth during the development of mouse molar teeth. J Periodontal Res, 2012, 47(1): 81-88.

[79] Thesleff I, Sharpe PT. Signalling networks regulating dental development. Mech Dev, 1997, 67(2): 111-123.

[80] Mikkola ML, Millar SE. The mammary bud as a skin appendage: unique and shared aspects of development. J Mam Gland Biol Neoplasia, 2006, 11(3/4): 187-203.

[81] Fuchs E. Scratching the surface of skin development. Nature, 2007, 22(7130): 834-842.