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Expression of Bone Morphogenetic Proteins and Msx Genes during Root Formation

¹ Developmental Biology Program, Institute of Biotechnology, Viikki Biocenter, PO Box 56, FIN-00014 University of Helsinki, Finland;
² current address, Department of Orthodontics, Graduate School of Medicine and Dentistry, Okayama University, Shikata-cho 2-5-1, Okayama 700-8525, Japan;

*corresponding author, yamat{at}md.okayama-u.ac.jp

	ABSTRACT

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Like crown development, root formation is also regulated by interactions between epithelial and mesenchymml tissues. Bone morphogenetic proteins (BMPs), together with the transcription factors Msx1 and Msx2, play important roles in these interactions during early tooth morphogenesis. To investigate the involvement of this signaling pathway in root development, we analyzed the expression patterns of Bmp2, Bmp3, Bmp4, and Bmp7 as well as Msx1 and Msx2 in the roots of mouse molars. Bmp4 was expressed in the apical mesenchyme and Msx2 in the root sheath. However, Bmps were not detected in the root sheath epithelium, and Msx transcripts were absent from the underlying mesenchyme. These findings indicate that this Bmp signaling pathway, required for tooth initiation, does not regulate root development, but we suggest that root shape may be regulated by a mechanism similar to that regulating crown shape in cap-stage tooth germs. Msx2 expression continued in the epithelial cell rests of Malassez, and the nearby cementoblasts intensely expressed Bmp3, which may regulate some functions of the fragmented epithelium.

KEY WORDS: epithelial-mesenchymal interactions • root development • dentinogenesis • cementogenesis

	INTRODUCTION

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Tooth development is characterized by sequential and reciprocal interactions between the dental epithelium and mesenchyme. Many signal molecules and growth factors have been implicated in the mediation of these interactions (Thesleff and Mikkola, 2002). Bone morphogenetic proteins (BMPs) are secretory signal molecules and members of the TGF-beta superfamily of growth and differentiation factors. During early tooth morphogenesis, the expression patterns of Bmp2, Bmp4, and Bmp7 are associated with the epithelial-mesenchymal interactions and shift between the tissues (Vainio et al., 1993; Åberg et al., 1997; Thesleff and Åberg, 1999). In organ culture, beads releasing BMP2 and BMP4 proteins mimic the inductive epithelial and mesenchymal signals. During tooth initiation, BMP4 induces the expression of Msx1 and Msx2 in dental mesenchyme (Vainio et al., 1993), and during bud- to cap-stage transition, it induces, in the epithelium, the expression of Msx2 as well as the formation of the enamel knot signaling center (Jernvall et al., 1998). Msx1 and Msx2 are homeobox-containing transcription factors, and their expression patterns are also associated with epithelial-mesenchymal interactions in early tooth development (MacKenzie et al., 1992; Jowett et al., 1993; Thesleff, 1995). Mice deficient for Msx1 or Msx2 show altered tooth phenotypes (Satokata and Maas, 1994; Satokata et al., 2000). Bmp4 is a major downstream target of Msx1 in the dental mesenchyme, and BMP can rescue the dental phenotype of Msx1 null mice (Bei et al., 2000). Hence. the BMP-Msx pathway mediates reciprocal interactions between the epithelium and mesenchyme during tooth initiation and crown morphogenesis.

After the tooth crown has formed, the outer and inner enamel epithelia form a double-layered Hertwig’s epithelial root sheath which proliferates apically and directs root morphogenesis. Histological observations indicate that there is a close association between the epithelial root sheath and the initiation of root dentin formation, and the peripheral pulpal mesenchymal cells differentiate into pre-odontoblasts along the inner surface of the epithelial root sheath. However, the molecular mechanisms regulating this interaction have not been identified in the process of root development (Thomas, 1995). As root formation proceeds, the epithelial root sheath disrupts, allowing mesenchymal cells from the dental follicle to come into contact with the root surface and differentiate into cementoblasts which deposit cementum (Thomas, 1995; Ten Cate, 1996). The function of this fragmented epithelium, known as epithelial cell rests of Malassez, is not known, but it has been speculated that it may induce cementoblast differentiation and perhaps later regulate their function (Thomas, 1995; Bosshardt and Schroeder, 1996; Kagayama et al., 1998).

The aim of this study was to investigate the possible roles of BMP signaling and Msx family transcription factors during root morphogenesis and the formation of root dentin and cementum. We performed an in situ hybridization analysis of temporospatial expression of Bmp2, Bmp3, Bmp4, Bmp7, Msx1, and Msx2. As a phenotypic marker for terminally differentiated mineralizing cells, we also analyzed the distribution of bone sialoprotein (Bsp) mRNA.

	MATERIALS & METHODS

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Processing of Tissues
The Animal Welfare Committee of the University of Helsinki approved the experimental procedures. Heads of 14-day-old NMRI mice were dissected in Dulbecco’s phosphate-buffered saline. The tissues were fixed in 4% paraformaldehyde at 4°C overnight, and decalcified in 12.5% EDTA containing 2.5% paraformaldehyde for 2 wks. They were dehydrated, embedded in paraffin, and serially sectioned at 7 µm. Keratin was used as a marker for epithelial cells, and it was detected by immunohistochemistry with polyclonal pan-keratin antibodies (DAKO, A575, Glostrup, Denmark) (Kaneko et al., 1999).

Probes and in situ Hybridization
The preparation of the Bmp2, Bmp3, Bmp4, Bmp7, Msx1, Msx2, and Bsp RNA probes has previously been described (Vainio et al., 1993; Vaahtokari et al., 1996; Kim et al., 1998). In situ hybridization of paraffin sections using ³⁵S-UTP-labeled riboprobe was performed as described previously (Vainio et al., 1993). The bright-field and dark-field images of each section were digitized, and the grains from dark fields were selected, colored red, and added to the bright-field pictures in Photoshop6 (Åberg et al., 1997; Jernvall et al., 1998; Kim et al., 1998).

	RESULTS

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Root Development
Fig. 1 shows the histological appearance of a sagittal section of the lower jaw of a 14-day-old mouse. In the section, 1st, 2nd, and 3rd molars show different stages of root development (Fig. 1A). The crowns of the 1st and 2nd molars are almost fully developed, and approximately one-half and one-third of the root has been formed in the 1st and 2nd molars, respectively. At the apical end of the growing root, epithelial root sheath is present. Odontoblasts are columnar cells lining the pulpal surface of dentin (Fig. 1B). In this study, we defined the apically located odontoblasts as "early odontoblasts" and the coronally located odontoblasts as "late odontoblasts". Pre-odontoblasts are the odontoblast precursors in the apical end of the root (Fig. 1B). We confirmed the identity of epithelium by immunohistochemistry using pan-keratin antibodies. Immunoreactivity was observed in the epithelial root sheath and the epithelial cell rests of Malassez. In the 3rd molar, root development has not been initiated, and the epithelial root sheath is continuous with the dental epithelium of the crown (Fig. 1C).

View larger version (161K): [in this window] [in a new window]   Figure 1. Sagittal section of molars in the lower jaw of a 14-day-old mouse. Histological appearance and keratin expression. (A) Hematoxylin and eosin staining. (B) Higher magnification of the distal root of 1st molar (inset in panel A). pod, pre-odontoblasts; eod, early odontoblast; od, odontoblasts; ce, cementoblasts; ob, osteoblasts. (C) Immunoreactivity to pan-keratin. Arrowhead indicates the epithelial cell rests of Malassez.

View larger version (204K): [in this window] [in a new window]   Figure 2. Localization of Bmp2 (A,B), Bmp3 (C,D), Bmp4 (E,F), and Bmp7 (G,H) in the molars of a 14-day-old mouse. Panels B, D, F, and H are high-magnification views of the distal root of the 1st molar as shown in panels A, C, E, and F, respectively. Small arrowhead, large arrowhead, and arrow indicate expression in odontoblasts, cementoblasts, and osteoblasts, respectively. od, odontoblasts; ce, cementoblasts; ob, osteoblasts; am, ameloblasts, ers, epithelial root sheath.

Bmp4 expression appeared early in the pre-odontoblastic cells adjacent to the epithelial root sheath (Figs. 2E, 2F). However, when pre-odontoblasts differentiated and started to secrete dentin matrix, Bmp4 expression was down-regulated almost completely (Fig. 2F). It was also expressed in ameloblasts (Fig. 2E). Bmp4 transcripts were also detected in the osteoblasts on the active bone-forming surface but with much weaker intensity than Bmp3 (Figs. 2E, 2F).

Bmp7 and Bmp4 were also detected in ameloblasts (Figs. 2E, 2G).

Expression of Msx1, Msx2, and Bsp
Msx1 was expressed in the dental pulp, and weakly in the alveolar bone and in the periodontal ligament-mesenchyme (Figs. 3A, 3B; Table). In contrast, Msx2 expression was very intense in the dental pulp, and no transcripts were detected in alveolar bone (Figs. 3C, 3D). At the apical end of the root, intense expression of Msx2 was observed in the epithelial root sheath. The signals were also observed in a patchy pattern in the periodontal ligament beneath the dentin surface (Figs. 3C, 3D). The similar distribution pattern of pan-keratin immunoreactive cells (Fig. 1C) indicated that Msx2 was expressed in the epithelial cell rests of Malassez. The pulpal mesenchyme in the apical end of the root, including the pre-odontoblasts lining the epithelial root sheath, was remarkably devoid of Msx1 and Msx2 transcripts (Figs. 3A, 3C).

View larger version (150K): [in this window] [in a new window]   Figure 3. Localization of Msx1 (A,B), Msx2 (C,D), and Bsp (bone sialoprotein) (E,F) in the molars of a 14-day-old mouse. Panels B, D, and F are high-magnification views of the distal root of the 1st molar as shown in panels A, C, and E, respectively. pu, pulp; pdl, periodontal ligament; ab, alveolar bone; od, odontoblasts; ce, cementoblasts; ob, osteoblasts; am, ameloblasts; ers, epithelial root sheath. Large arrow, small arrow, and arrowhead indicate the expression in odontoblasts, cementoblasts, and Malassez epithelial cell rests, respectively.

	DISCUSSION

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All four BMPs examined showed dynamic expression patterns and were associated with root morphogenesis and/or differentiation of the hard-tissue-forming cells. All BMPs were expressed in the odontoblast lineage cells at some stage. Bmp4 and Bmp7 were expressed in ameloblasts, and only Bmp3 was found in cementoblasts. Of the Msx genes, Msx2 was associated with both morphogenesis and ameloblast differentiation, whereas Msx1 showed very weak expression in pulp mesenchyme with no obvious association with root development. The findings indicate that some but not all functions of these genes are similar in crown and root development.

During the initiation of tooth morphogenesis, BMP2, BMP4, and BMP7 act as important epithelial signals regulating the differentiation of the neural-crest-derived mesenchyme into odontogenic lineage (Thesleff and Åberg, 1999). BMPs induce in the mesenchyme the expression of Msx1 and Msx2 (Vainio et al., 1993). The functions of these two genes are redundant in early stages in tooth development, since, in single-gene knockouts, tooth development is normal until the bud stage, whereas in double knockouts, tooth morphogenesis is arrested at the dental lamina stage (Bei and Maas, 1998). Interestingly, Msx1 and Msx2 transcripts were completely absent from the apical part of the root mesenchyme, and transcripts of Bmps were not detected in the epithelium of the root sheath. These findings indicate that BMPs and Msx1 and Msx2 do not have similar functions in root and crown initiation. Apparently, the induction of mesenchyme by epithelial BMPs during tooth initiation—‘odontogenic competence’—is maintained during root development (Vainio et al., 1993; Tucker et al., 1998).

Msx1 mutant tooth development arrests at the bud stage (Satokata and Maas, 1994). At this time, Msx2 has been down-regulated in the mesenchyme (Jowett et al., 1993), and therefore it does not compensate for the function of Msx1. An important function of Msx1 in the mesenchyme is to regulate the expression of Bmp4, which acts as a reciprocal signal on epithelium and regulates the development of the enamel knot. The genes regulated by BMP4 in the enamel knot include Msx2 and p21. The enamel knot acts as a signaling center which regulates subsequent epithelial morphogenesis during the cap stage (Jernwall et al., 1998; Thesleff and Åberg, 1999; Bei et al., 2009). This primary enamel knot as well as the later-forming secondary enamel knots regulate the complex epithelial folding morphogenesis which determines the cusp pattern of the crown (Jernvall and Thesleff, 2000). Interestingly, Bmp4 was expressed in the mesenchyme lining the root sheath epithelium, which in turn expressed Msx2. This may be indicative of a similar mesenchymal-epithelial interaction regulating epithelial morphogenesis in both the crown and the root. Like the crown shape, the shape of the root is complicated, particularly in the multirooted molar teeth.

Interestingly, during the preparation of this manuscript, Ohshima et al. (2002) reported that Msx2 null mutant mice have irregularly shaped molar roots. This provides direct evidence that Msx2 is involved in root morphogenesis. Classic heterotypic tissue recombination experiments between molars and incisors have shown that, besides crown morphogenesis, the mesenchyme also directs root development (Kollar and Baird, 1970). Therefore, it is conceivable that mesenchymal factors regulate the growth and morphogenesis of the root sheath epithelium which determines the root shape. We suggest that BMP4 and Msx2 are involved in the mediation of this mesenchymal-epithelial interaction.

BMPs were expressed sequentially at different stages of odontoblast differentiation. Bmp4 was expressed in the early pre-odontoblasts lining the root sheath epithelium. Subsequently, Bmp2 and Bmp7 were expressed in pre-odontoblasts and odontoblasts during a relatively short period of differentiation and were absent from mature odontoblasts on both crown and root dentin surfaces. Bmp3 was expressed in the pre-odontoblasts and odontoblasts in the root area, but it was absent from differentiating and secretory odontoblasts in the crown, as previously reported (Åberg et al., 1997). As suggested for BMP4, BMP2, and BMP7 may affect epithelial differentiation (Tabata et al., 2002). All BMPs may also have autocrine or paracrine effects on differentiating odontoblasts.

Bmp3 was expressed intensely in the dental follicle cells in the root area, as earlier reported in the crown follicle (Åberg et al., 1997). Particularly intense Bmp3 expression was found in cementoblasts. In addition, it was intensely expressed in osteoblasts at sites of active deposition. BMP3 may regulate the function of the osteoblasts and cementoblasts. It is a negative regulator of trabecular bone formation, and in vitro findings indicate an inhibitory role for BMP3 in BMP2-mediated differentiation of osteoprogenitor cells into osteoblasts (Daluiski et al., 2001). It is possible that BMP3 has a similar inhibitory function in cementum formation. A possible target of BMP regulation is bone sialoprotein, which was co-expressed with Bmp2, Bmp3, and Bmp7 in differentiating odontoblasts and with Bmp3 in cementoblasts and osteoblasts. Expression of Bsp by osteoblasts on the active bone-forming surface as well as by cementoblasts has been demonstrated previously (D’Errico et al., 1997). Our careful analysis showed that Bsp expression was restricted to the apical differentiating pre-odontoblasts and that it was down-regulated with advancement of the differentiation, while other matrix proteins such as osteocalcin and type I collagen show intense expression in all odontoblasts during similar developmental stages (D’Errico et al., 1997).

The differentiation of cementoblasts from dental follicle cells, and their deposition of cementum at the dentin surface, is believed to be regulated by the epithelial cells derived from the root sheath, i.e., the cell rests of Malassez (Thomas, 1995). None of the BMPs analyzed was expressed by the Malassez epithelial cells, and therefore the putative signal remains to be identified. However, the close association between the Bmp3-expressing cementoblasts and Msx2-expressing Malassez epithelial cells raises the possibility that perhaps cementoblasts signal to the Malassez epithelial cells and regulate their functions. Msx2 has previously been associated with the maintenance of the proliferative potential and inhibition of differentiation (Hu et al., 2001). It is an intriguing possibility that Msx2 has a similar function in Malassez epithelial cells, which do not proliferate and stay apparently undifferentiated. The earlier observation that the epithelial cell-rest cells bind EGF intensely is in line with this proposal (Thesleff, 1987). Very little is currently known of the roles of the Malassez epithelial cells and the patterns of their gene expression (Yamashiro et al., 2000).

	ACKNOWLEDGMENTS

 
We thank Merja Mäkinen and Riikka Santalahti for excellent technical assistance. This study was supported by the Academy of Finland and the Sigrid Juselius Foundation. T. Yamashiro was supported by the Graduate School of Medicine and Dentistry, Okayama University, Japan.

Received May 31, 2002; Last revision December 16, 2002; Accepted December 17, 2002

	REFERENCES

TOP ABSTRACT INTRODUCTION MATERIALS & METHODS RESULTS DISCUSSION REFERENCES

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

Bei M, Maas R (1998). FGFs and BMP4 induce both Msx1-independent and Msx1-dependent signaling pathways in early tooth development. Development 125:4325–4333.[Abstract]

Bei M, Kratochwil K, Maas RL (2000). BMP4 rescues a non-cell-autonomous function of Msx1 in tooth development. Development 127:4711–4718.[Abstract]

Bosshardt DD, Schroeder HE (1996). Cementogenesis reviewed: a comparison between human premolars and rodent molars. Anat Rec 245:267–292.[Medline]

D’Errico JA, MacNeil RL, Takata T, Berry J, Strayhorn C, Somerman MJ (1997). Expression of bone associated markers by tooth root lining cells, in situ and in vitro. Bone 20:117–126.[Medline]

Daluiski A, Engstrand T, Bahamonde ME, Gainer LW, Agius E, Stevenson SL, et al. (2001). Bone morphogenetic protein-3 is a negative regulator of bone density. Nat Genet 27:84–88.[ISI][Medline]

Hu G, Lee H, Price SM, Shen MM, Abate-Shen C (2001). Msx homeobox genes inhibit differentiation through upregulation of cyclin D1. Development 128:2373–2384.[Abstract/Free Full Text]

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

Jernvall J, Åberg T, Kettunen P, Keranen S, Thesleff I (1998). The life history of an embryonic signaling center: BMP-4 induces p21 and is associated with apoptosis in the mouse tooth enamel knot. Development 125:161–169.[Abstract]

Jowett AK, Vainio S, Ferguson MW, Sharpe PT, Thesleff I (1993). Epithelial-mesenchymal interactions are required for msx 1 and msx 2 gene expression in the developing murine molar tooth. Development 117:461–470.[Abstract]

Kagayama M, Sasano Y, Zhu J, Hirata M, Mizoguchi I, Kamakura S (1998). Epithelial rests colocalize with cementoblasts forming acellular cementum but not with cementoblasts forming cellular cementum. Acta Anat 163:1–9.[ISI][Medline]

Kaneko H, Hashimoto S, Enokiya Y, Ogiuchi H, Shimono M (1999). Cell proliferation and death of Hertwig’s epithelial root sheath in the rat. Cell Tissue Res 298:95–103.[ISI][Medline]

Kim HJ, Rice DP, Kettunen PJ, Thesleff I (1998). FGF-, BMP- and Shh-mediated signalling pathways in the regulation of cranial suture morphogenesis and calvarial bone development. Development 125:1241–1251.[Abstract]

Kollar EJ, Baird GR (1970). Tissue interactions in embryonic mouse tooth germs. II. The inductive role of the dental papilla. J Embryol Exp Morphol 24:173–186.[ISI][Medline]

MacKenzie A, Ferguson MW, Sharpe PT (1992). Expression patterns of the homeobox gene, Hox-8, in the mouse embryo suggest a role in specifying tooth initiation and shape. Development 115:403–420.[Abstract]

Ohshima H, Maeda T, Satokata I, Maas R (2002). Functional significance of Msx2 gene during tooth development. In: Proceedings of the International Conference on the Dentin Pulp Complex 2001. Chicago: Quintessence, pp. 11-14.

Satokata I, Maas R (1994). Msx1 deficient mice exhibit cleft palate and abnormalities of craniofacial and tooth development. Nat Genet 6:348–356.[ISI][Medline]

Satokata I, Ma L, Ohshima H, Bei M, Woo I, Nishizawa K, et al. (2000). Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation. Nat Genet 24:391–395.[ISI][Medline]

Tabata MJ, Fujii T, Liu JG, Ohmori T, Abe M, Wakisaka S, et al. (2002). Bone morphogenetic protein 4 is involved in cusp formation in molar tooth germ of mice. Eur J Oral Sci 110:114–120.[ISI][Medline]

Ten Cate AR (1996). The role of epithelium in the development, structure and function of the tissues of tooth support. Oral Dis 2:55–62.[Medline]

Thesleff I (1987). Epithelial cell rests of Malassez bind epidermal growth factor intensely. J Periodontal Res 22:419–421.[ISI][Medline]

Thesleff I (1995). Homeobox genes and growth factors in regulation of craniofacial and tooth morphogenesis. Acta Odontol Scand 53:129–134.[ISI][Medline]

Thesleff I, Åberg T (1999). Molecular regulation of tooth development. Bone 25:123–125.[Medline]

Thesleff I, Mikkola M (2002). The role of growth factors in tooth development. Int Rev Cytol 217:93–135.[ISI][Medline]

Thomas HF (1995). Root formation. Int J Dev Biol 39:231–237.[ISI][Medline]

Tucker AS, Matthews KL, Sharpe PT (1998). Transformation of tooth type induced by inhibition of BMP signaling. Science 282:1136–1138.[Abstract/Free Full Text]

Vaahtokari A, Åberg T, Jernvall J, Keranen S, Thesleff I (1996). The enamel knot as a signaling center in the developing mouse tooth. Mech Dev 54:39–43.[ISI][Medline]

Vainio S, Karavanova I, Jowett A, Thesleff I (1993). Identification of BMP-4 as a signal mediating secondary induction between epithelial and mesenchymal tissues during early tooth development. Cell 75:45–58.[ISI][Medline]

Yamashiro T, Fujiyama K, Fukunaga T, Wang Y, Takano-Yamamoto T (2000). Epithelial rests of Malassez express immunoreactivity of TrkA and its distribution is regulated by sensory nerve innervation. J Histochem Cytochem 48:979–984.[Abstract/Free Full Text]

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This Article Abstract Figures Only Full Text (PDF) Services Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (37) Citing Articles via Google Scholar Google Scholar Articles by Yamashiro, T. Articles by Thesleff, I. Search for Related Content PubMed PubMed Citation Articles by Yamashiro, T. Articles by Thesleff, I.