CLINICAL REVIEW

 

Recent perspectives vis-á-vis the biological basis of tooth eruption

 

 

S Nel^I; HD Hendrik^II; SC Boy^III; EJ Raubenheimer^IV

^IBChD, MSc: Department of Oral Pathology and Oral Biology, School of Dentistry, Faculty of Health Sciences, University of Pretoria, Oral and Dental Hospital, Bophelo Road, Pretoria
^IIBDS, MSc: Department of Oral Pathology and Oral Biology, Sefako Makgatho Health Sciences University, Medunsa Campus, Setlogelo Drive, Ga-Rankuwa
^IIIBChD, MChD(Oral Path), PhD: Department of Oral Pathology and Oral Biology, Sefako Makgatho Health Sciences University, Medunsa Campus, Setlogelo Drive, Ga-Rankuwa
^IVPhD, DSc: Department of Oral Pathology and Oral Biology, Sefako Makgatho Health Sciences University, Medunsa Campus, Setlogelo Drive, Ga-Rankuwa

Correspondence

 

 

---

ABSTRACT

A thorough understanding of recent advancements regarding the molecular interactions responsible for tooth eruption is indispensable to all dental specialties and may provide insight for treating clinical eruption disorders. The biological processes responsible for tooth eruption have long been a matter of debate. Several types of cells of dental origin and numerous molecular factors that were believed to be responsible for this process have repeatedly been considered and investigated. Most existing eruption theories have concentrated on selective cells or processes as the sole generating forces of tooth eruption. This article reviews previously proposed eruption theories, in the light of significant advances in the understanding that the sequential interactions between dental epithelium and ectomesenchymal cells pattern the initiating cascade of the eruption process. These findings are presented in the context of tooth development within the milieu of a changing bony socket. Understanding the process of tooth eruption in this framework points to the fact that tooth eruption is essentially a stage of tooth development which, through selective resorption and deposition of bone, allows the developing tooth to be displaced through the alveolar bone to its position of function in the oral cavity.

Key words: tooth eruption, dental follicle, paracrine signaling, bone remodeling

---

 

 

INTRODUCTION

Tooth movements during the lifetime of an individual can generally be divided into pre-eruptive, eruptive and post-eruptive phases. For the purpose of this overview we will focus on the eruptive phase only. Tooth movements

during this phase are subdivided into intra-osseous and supra-osseous stages referring to the movement of the tooth from a position within the bone to its functional position in occlusion.¹ Tooth eruption is a complex process in which the interplay of several tissues and mechanisms have been proposed. All the tissues within the vicinity of the tooth, and thought to be capable of generating some kind of force, have been implicated as contributing to the process of tooth eruption.² Common theories of dental eruption include hydrostatic pressure, the periodontal ligament, root formation and elongation, selective bone resorption and formation, and the role of the dental follicle surrounding the developing tooth.

The purpose of this article is to review the previously proposed mechanisms of tooth eruption as a platform for presenting the newest significant findings regarding the intricate interplay of inductive signals between the dental follicle, reduced enamel epithelium, stellate reticulum and alveolar bone in the process of tooth eruption.

 

HISTORICAL THEORIES

The hydrostatic pressure theory is one of the oldest tooth eruption theories known.^3-5 According to this theory, blood pressure exerted in the vascular tissue between a developing tooth and its bony surroundings creates a mechanical force causing tooth eruption.⁵ Although a pressure gradient from apical to occlusal was revealed in the teeth of dogs,⁶ this theory was contradicted by studies which proved hypotensive drugs³ and hemodynamic influences such as changes in pulse rate and blood pressure⁷ to not have any effect on tooth eruption. Other studies on human and rat teeth respectively propose contradictory mechanisms and therefore this theory remains inconclusive.^8,9,10,11

Fibroblasts and collagen fibers of the periodontal ligament have long been implicated as generating the eruptive force for tooth eruption.^12-18 The proliferation and subsequent occlusal migration of these periodontal ligament fibroblasts have been proposed as main factors responsible for tooth eruption.^15,18 Periodontal fibroblasts in an in vivo situation of eruption exhibit characteristics of cells actively synthesizing and secreting protein rather than those of motile or contractile cells as described by these studies. The role of collagen has also been investigated,¹⁹ but the use of sodium morrhuate, known to reduce production and maturation of collagen, had no effect on the process of eruption.²⁰ Collagen remodeling has been proposed to be a crucial factor in tooth eruption²¹ and the lack of matrixmetalloproteinases (MMPs) seems to be related to abnormal tooth eruption in humans.²² Collagen, its synthesis, remodeling and the cells implicated in these processes can however not be accepted as the sole mediators of tooth eruption as a tooth without a periodontal ligament can still erupt.²³ It is however possible that the periodontal ligament could play a role in the supra-osseous phase of the eruptive process in lifting the tooth into the occlusal plane.²⁴

The theory that root formation results in tooth eruption seems plausible as both processes take place simultane-ously.^23,25 It seems logical that root formation and subsequent elongation would result in extrusion of the tooth from the bony socket. It has however been proven by studies in dogs and mice that rootless teeth do erupt and that teeth may also sometimes erupt a greater distance than the length of the roots.^1,26-29 Pressure applied to bone generally results in bone resorption.³⁰ Therefore, if root elongation was indeed responsible for "pushing" the tooth into occlusion as the root elongates, it would mean that pressure would have to be applied to the bone by the elongating root. The force generated by this kind of pressure would definitely result in bone resorption at the apical base. Therefore root formation is accommodated during tooth eruption and can be regarded as a consequence, rather than a cause, of the process.^31,32

The dental follicle (DF) refers to the condensed ectomes-enchyme encapsulating the unerupted, developing tooth. (Figure 1) It was demonstrated, as early as 1980, that once the DF of unerupted teeth were surgically removed, those teeth failed to erupt.²⁹ When a developing unerupted premolar tooth was surgically removed and replaced with a metal replica, the replica erupted, provided that the DF was retained.²⁷ These studies clearly demonstrate the essential role of the DF in the process of tooth eruption, while simultaneously eliminating the role of other tissues such as the dental pulp, periodontal ligament and root formation.

 

 

Regional differences in the DF were described following further studies on dog premolars.³³ If the basal (apical) half of the DF was left intact and the coronal half was removed, alveolar bone resorption did not occur, an eruption path did not form and the tooth eruption was impeded.³³ Conversely, if the coronal half was left intact and the basal half removed, bone resorption did occur at the coronal aspect, but the tooth did not erupt as no bone was formed at the base of the tooth socket.³³ Therefore this study suggested that the coronal aspect of the DF regulates osteoclastogenesis (bone resorption) and the basal aspect of the DF is responsible for osteogenesis (bone formation); both processes essential for tooth eruption.³³ Regional differences in gene expression of the DF were assessed using laser capture microdissection.³⁴ The coronal and basal halves of the DFs of rat first mandibular molars were isolated and RNA extracted from both halves respectively.³⁴ Real time reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression of marker genes for bone resorption (osteoclastogenesis) and bone formation (osteogenesis).³⁴ The receptor activator of nuclear factor kappa B ligand (RANKL) gene was utilised as a marker gene for osteoclastogenesis, therefore for bone resorption. Bone morphogenetic protein-2 (BMP-2) gene served as a marker for osteogenesis or bone formation. The results showed a higher expression of bone-resorption genes (RANKL) in the coronal half of the DF,³⁴ but higher expression of bone-formation genes (BMP-2) in the basal half of the follicle.³⁴ Therefore, clearly, the DF regulates bone formation and resorption via spatial expression of different genes at different levels and times.

Current concepts regarding the paracrine signaling role of the dental follicle in tooth eruption

Tooth development is initiated and crown and root development regulated by a cascade of reciprocal interactions between the dental epithelium and the dental mesenchyme.^35,36

Correspondingly, the process of tooth eruption is represented by a cascade of cellular events leading to the recruitment of monocytes to the dental follicle followed by osteoclastogenesis and bone resorption, a prerequisite for tooth eruption.³⁷ This cascade of molecular events is initiated by epithelial-ectomesenchymal interactions between the dental follicle, the reduced enamel epithelium (REE) and the stellate reticulum (Figure 2).³⁶ The REE consists of the layer of ameloblasts fused with the stratum intermedium, stellate reticulum and the outer enamel epithelium upon completion of crown formation.¹

 

 

Apoptosis of epithelial cells of the stellate reticulum, stratum intermedium and ameloblast layer during the advanced stages of enamel secretion have been reported.³⁸ This apoptotic process is believed to have a direct influence on osteoclastogenesis through the release of interleukin-1α (IL-1 α) by the cells of the stellate reticulum, the receptors for which are located on the cells of the dental follicle.³⁷ IL-1 a subsequently stimulates the expression of colony-stimulating factor-1 (CSF-1) and monocyte chemotactic protein-1 (MCP-1) within the cells of the dental follicle, thereby allowing the dental follicle to act as a chemoatractant for monocytes.^37,39 The stellate reticulum cells also participate in osteoclastogenesis by releasing parathyroid hormone-related protein (PTHrP) which further increases the expression of both MCP-1 and CSF-1.⁴⁰ Concurrently with osteoclastogenesis, CSF-1 down-regulates the expression of osteoprotegerin (OPG), a well-known decoy receptor for RANKL which would normally inhibit osteoclast differentiation.⁴¹ The cells of the REE and stellate reticulum therefore jointly exert a paracrine effect on the cells of the dental follicle, enhancing the expression of chemoattractant molecules.⁴² Additionally, the REE also secretes proteases that aid in creating an eruption pathway for the tooth through enzymatic digestion of collagens.^43,44 Other molecules such as epidermal growth factor (EGF) and transforming growth factor β 1 (TGF-β1) released by the cells of the dental follicle further enhance the expression of CSF-1 within the dental follicle.^45-47 Paracrine signalling involving both the ectomesenchyme derived dental follicle and epithelial cells of the REE and stellate reticulum are therefore the key role players in the process of tooth eruption. In the study, conducted in 1984, where tooth crowns were removed and replaced with metal or silicone replicas which "erupted" into the oral cavities, the authors did not specifically mention whether the REE of the 15 week old beagle dogs was retained or removed with the tooth crowns during the study.²⁷ If we assume that the REE was removed during the procedure, we propose that the dental follicles associated with the metal replicas had already received signalling from the epithelial cells at the stage of surgical intervention. Signalling for monocyte attraction to the area of resorption had therefore already been accomplished at that stage, which apparently allowed eruption of the object.

Bone resorption with the creation of an eruption path-way is however not sufficient for the displacement of the tooth from its bony crypt into occlusion. Coronal bone resorption is therefore coupled with apical bone formation resulting in the physical displacement of the erupting tooth. The dental follicle cells located in the basal aspect express bone morphogenic proteins 2 and 3 (BMP 2 and BMP 3) responsible for the promotion of bone formation.⁴⁸ The expression of these BMP's is greatly enhanced by tumour necrosis factor-a (TNF-α) expression in the dental follicle cells.⁴⁸ TNF-a expression is maximally upregulated in the rat dental follicle when rapid bone deposition occurs at the base of the tooth crypt.⁴⁸ The cascade of signalling events associated with tooth eruption at the apical aspect of the developing tooth, have not been completely elucidated.⁴⁹ Further studies are required to shed some light on the reciprocal signalling between the epithelial root sheath cells and the associated dental follicle during the eruptive process.

 

CONCLUSION

Tooth eruption represents a series of precisely regulated cascades of paracrine signaling events between epithelial cells of the enamel organ and ectomesenchymal cells of the dental follicle. These tightly regulated processes which bring about selective alveolar bone resorption in the coronal aspects of the erupting tooth and bone formation in the apical aspects of the tooth, are considered central to the process of tooth eruption.

The authors thus propose that tooth eruption should be regarded as a stage of tooth development which, through epithelial-ectomesenchymal interactions, represents the very mechanism that allows the dental follicle to assume its fundamental role in the process of selective bone remodeling required for the movement of a tooth from its developmental position in bone to its functional position in the oral cavity.

 

ACRONYMS

BMP-2: Bone Morphogenetic Protein-2

CSF-1: Colony-stimulating Factor-1

DF: Dental Follicle

EGF: Epidermal Growth Factor

ERS: Epithelial Root Sheath

IL-1α : Interleukin-1 α

MCP-1: Monocyte Chemotactic Protein-1

MMPs: Matrixmetalloproteinases

RANKL: Receptor Activator of Nuclear factor Kappa B Ligand

REE: Reduced Enamel Epithelium

TNF- α: Tumour Necrosis Factor-a

 

References

1. Nanci A. Ten Cate's Oral Histology: Development, Structure and Function, Eighth edition : Elsevier, 2013.         [ Links ]

2. Berkovitz BKB, Holland GR, Moxham BJ. Oral Anatomy, Histology and Embryology, Fourth edition : Elsevier, 2009.         [ Links ]

3. Main JH, Adams D. Experiments on the rat incisor into the cellular proliferation and blood-pressure theories of tooth eruption. Arch Oral Biol 1966;11(2):163-78.         [ Links ]

4. Sutton PR, Graze HR. The blood-vessel thrust theory of tooth eruption and migration. Med Hypotheses 1985;18(3):289-95.         [ Links ]

5. Constant T. The mechanical factor in the eruption of the teeth, hitherto unrecognized. Journal of the British Dental Association 1896(17):723-32.         [ Links ]

6. Van Hassel HJ, McMinn RG. Pressure differential favouring tooth eruption in the dog. Arch Oral Biol 1972;17(1):183-90.         [ Links ]

7. Risinger RK, Proffit WR. Continuous overnight observation of human premolar eruption. Arch Oral Biol 1996;41(8-9):779-89.         [ Links ]

8. Shimada A, Komatsu K, Chiba M. Effects of local injections of vasoactive drugs on eruption rate of incisor teeth in anaesthetized rats. Arch Oral Biol 2006;51(6):449-56.         [ Links ]

9. Cheek CC, Paterson RL, Proffit WR. Response of erupting human second premolars to blood flow changes. Arch Oral Biol 2002;47(12):851-8.         [ Links ]

10. Shimada A, Shibata T, Komatsu K. Relationship between the tooth eruption and regional blood flow in angiotensin II-induced hypertensive rats. Arch Oral Biol 2004;49(6):427-33.         [ Links ]

11. Wise GE, King GJ. Mechanisms of tooth eruption and orthodontic tooth movement. J Dent Res 2008;87(5):414-34.         [ Links ]

12. Berkovitz BK, Thomas NR. Unimpeded eruption in the root-resected lower incisor of the rat with a preliminary note on root transection. Arch Oral Biol 1969;14(7):771-80.         [ Links ]

13. Moxham BJ, Berkovitz BK. The effects of root transection on the unimpeded eruption rate of the rabbit mandibular incisor. Arch Oral Biol 1974;19(10):903-9.         [ Links ]

14. Beertsen W, Everts V, van den Hooff A. Fine structure of fibroblasts in the periodontal ligament of the rat incisor and their possible role in tooth eruption. Arch Oral Biol 1974;19(12):1087-98.         [ Links ]

15. Perera KA, Tonge CH. Fibroblast cell population kinetics in the mouse molar periodontal ligament and tooth eruption. J Anat 1981;133(Pt 2):281-300.         [ Links ]

16. Bellows CG, Melcher AH, Aubin JE. An in-vitro model for tooth eruption utilizing periodontal ligament fibroblasts and collagen lattices. Arch Oral Biol 1983;28(8):715-22.         [ Links ]

17. Kasugai S, Suzuki S, Shibata S, Yasui S, Amano H, Ogura H. Measurements of the isometric contractile forces generated by dog periodontal ligament fibroblasts in vitro. Arch Oral Biol 1990;35(8):597-601.         [ Links ]

18. Weinreb M, Gal D, Weinreb MM, Pitaru S. Changes in the shape and orientation of periodontal ligament fibroblasts in the continuously erupting rat incisor following removal of the occlusal load. J Dent Res 1997;76(10):1660-6.         [ Links ]

19. Taverne AA. Collagen responsible for tooth eruption? A study of the eruption of rat incisors. Aust Orthod J 1993;12(4):199-206.         [ Links ]

20. Marks SC, Jr., Larson EK, Wise GE, Gorski JP. Collagen metabolism and tooth eruption: the effects of sodium morrhuate infusions on premolar eruption in dogs. Schweiz Monatsschr Zahnmed 1995;105(8):1029-32.         [ Links ]

21. Beertsen W, Holmbeck K, Niehof A, Bianco P, Chrysover-gis K, Birkedal-Hansen H, et al. On the role of MT1-MMP, a matrix metalloproteinase essential to collagen remodeling, in murine molar eruption and root growth. Eur J Oral Sci 2002;110(6):445-51.         [ Links ]

22. Kim SG, Kim MH, Chae CH, Jung YK, Choi JY. Downregulation of matrix metalloproteinases in hyperplastic dental follicles results in abnormal tooth eruption. BMB Rep 2008;41(4):322-7.         [ Links ]

23. Proffit WR, Frazier-Bowers SA. Mechanism and control of tooth eruption: overview and clinical implications. Orthod Craniofac Res 2009;12(2):59-66.         [ Links ]

24. Wise GE. Cellular and molecular basis of tooth eruption. Orthod Craniofac Res 2009;12(2):67-73.         [ Links ]

25. Yoo HI, Kang JH, Yang SY, Yong JH, Moon JS, Kim MS, et al. Differential expression of cxcl-14 during eruptive movement of rat molar germs. J Exp Zool B Mol Dev Evol 2011 .April, 1        [ Links ]

26. Kim TH, Bae CH, Lee JC, Ko SO, Yang X, Jiang R, et al. betacatenin is required in odontoblasts for tooth root formation. J Dent Res 2013;92(3):215-21.         [ Links ]

27. Marks SC, Jr., Cahill DR. Experimental study in the dog of the non-active role of the tooth in the eruptive process. Arch Oral Biol 1984;29(4):311-22.         [ Links ]

28. Shapira Y, Kuftinec MM. Rootless eruption of a mandibular permanent canine. Am J Orthod Dentofacial Orthop 2011;139(4):563-6.         [ Links ]

29. Cahill DR, Marks SC, Jr. Tooth eruption evidence for the central role of the dental follicle. J Oral Pathol 1980;9(4):189-200.         [ Links ]

30. Chole RA, McGinn MD, Tinling SP. Pressure-induced bone resorption in the middle ear. Ann Otol Rhinol Laryngol 1985;94(2 Pt 1):165-70.         [ Links ]

31. Marks SC, Jr., Schroeder HE. Tooth eruption: theories and facts. Anat Rec 1996;245(2):374-93.         [ Links ]

32. Wang XP. Tooth eruption without roots. J Dent Res 2013;92(3):212-4.         [ Links ]

33. Marks SC, Jr., Cahill DR. Regional control by the dental follicle of alterations in alveolar bone metabolism during tooth eruption. J Oral Pathol 1987;16(4):164-9.         [ Links ]

34. Wise GE, Yao S. Regional differences of expression of bone morphogenetic protein-2 and RANKL in the rat dental follicle. Eur J Oral Sci 2006;114(6):512-6.         [ Links ]

35. Becktor KB, Nolting D, Becktor JP, Kjaer I. Immunohistochemical localization of epithelial rests of Malassez in human periodontal membrane. Eur J Orthod 2007;29(4):350-3.         [ Links ]

36. Vaahtokari A, Vainio S, Thesleff I. Associations between transforming growth factor beta 1 RNA expression and epithelialmesenchymal interactions during tooth morphogenesis. Development 1991;113(3):985-94.         [ Links ]

37. Wise GE, Zhao L, Grier RLt. Localization and expression of CSF-1 receptor in rat dental follicle cells. J Dent Res 1997;76(6):1244-9.         [ Links ]

38. Vaahtokari A, Aberg T, Thesleff I. Apoptosis in the developing tooth: association with an embryonic signaling center and suppression by EGF and FGF-4. Development 1996;122(1):121-9.         [ Links ]

39. 39. Wise GE, Lin F, Zhao L. Transcription and translation of CSF-1 in the dental follicle. J Dent Res 1995;74(9):1551-7.         [ Links ]

40. Wise GE, Que BG, Huang H, Lumpkin SJ. Enhancement of gene expression in rat dental follicle cells by parathyroid hormone-related protein. Arch Oral Biol 2000;45(10):903-9.         [ Links ]

41. Wise GE, Ren Y, Yao S. Regulation of osteoprotegerin gene expression in dental follicle cells. J Dent Res 2003;82(4):298-302.         [ Links ]

42. Wise GE, Marks SC, Jr., Zhao L. Effect of CSF-1 on in vivo expression of c-fos in the dental follicle during tooth eruption. Eur J Oral Sci 1998;106 Suppl 1:397-400.         [ Links ]

43. Park SJ, Bae HS, Cho YS, Lim SR, Kang SA, Park JC. Apoptosis of the reduced enamel epithelium and its implications for bone resorption during tooth eruption. J Mol Histol 2013;44(1):65-73.         [ Links ]

44. Omar NF, Gomes JR, Neves Jdos S, Salmon CR, Novaes PD. MT1-MMP expression in the odontogenic region of rat incisors undergoing interrupted eruption. J Mol Histol 2011;42(6):505-11.         [ Links ]

45. Shroff B, Kashner JE, Keyser JD, Hebert C, Norris K. Epidermal growth factor and epidermal growth factor-receptor expression in the mouse dental follicle during tooth eruption. Arch Oral Biol 1996;41(6):613-7.         [ Links ]

46. Fox SW, Lovibond AC. Current insights into the role of transforming growth factor-beta in bone resorption. Mol Cell Endocrinol 2005;243(1-2):19-26.         [ Links ]

47. Wise GE, Lin F, Fan W. Effects of transforming growth factor-beta 1 on cultured dental follicle cells from rat mandibular molars. Arch Oral Biol 1992;37(6):471-8.         [ Links ]

48. Yao S, Prpic V, Pan F, Wise GE. TNF-alpha upregulates expression of BMP-2 and BMP-3 genes in the rat dental follicle--implications for tooth eruption. Connect Tissue Res 2010;51(1):59-66.         [ Links ]

49. Bradaschia-Correa V, Casado-Gomez I, Moreira MM, Ferreira LB, Arana-Chavez VE. Immunolocalization of Smad-4 in developing molar roots of alendronate-treated rats. Arch Oral Biol 2013;58(11):1744-50.         [ Links ]

 

 

Correspondence:
S Nel
PO Box 1266, Pretoria, 0001
Tel: 012 319 2664
Fax: 012 321 2225
Cell: 082 772 4511
E-mail: sulette.nel@up.ac.za