Immunolocalization of BMP-2/-4, FGF-4, and WNT10b in the Developing Mouse First Lower Molar

Nadiri, Amal; Kuchler‐Bopp, Sabine; Haïkel, Youssef; Lesot, Hervé

doi:10.1177/002215540405200110

Cited by 70 publications

(85 citation statements)

References 48 publications

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“…Among them, BMP-2 is one of the most crucial for regulating epithelial-mesenchymal interactions and is expressed in the primary enamel knot, which is an epithelial signaling center and plays a central role in tooth morphogenesis (9,27). In tooth development, DSPP is a marker of odontoblast differentiation and is associated with dentin mineralization.…”

Section: Discussionmentioning

confidence: 99%

The Canonical BMP Signaling Pathway Plays a Crucial Part in Stimulation of Dentin Sialophosphoprotein Expression by BMP-2

Cho

Yoon

Woo

et al. 2010

Journal of Biological Chemistry

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Dentin sialophosphoprotein (DSPP), a typical dentin-specific protein, is mainly expressed in the dentin extracellular matrix and plays a role in dentin mineralization. BMP-2 provides a strong signal for differentiation and mineralization of odontoblasts and osteoblasts. Previously, BMP-2 treatment is reported to stimulate Dspp expression in the MD10-F2 pre-odontoblast cells through activation of the heterotrimeric transcription factor Y (NF-Y). The canonical BMP signaling pathway is known to contribute greatly to biomineralization, however, it is not known whether it is involved in Dspp expression. Here, we investigated this question. Activation of the canonical BMP-2 signaling pathway in MDPC-23, preodontoblast cell, by overexpression of constitutively active Smad1/5 or downstream transcription factors Dlx5 and Runx2 stimulated Dspp expression. Conversely, knockdown of each element with siRNA significantly blocked the BMP-2-induced Dspp expression. To test whether these transcription factors downstream of BMP-2 are directly involved in regulating Dspp, we analyzed the mouse Dspp promoter. There are 5 well conserved homeodomain binding elements, H1 to H5, in Dspp proximal promoter regions (؊791 to ؉54). A serial deletion of H1 and H2 greatly changed basal promoter activity and responsiveness to Dlx5 or Msx2. However, further deletions did not change the responsiveness to Dlx5 or Msx2. H1 and H2 sites can be suggested as specific response elements of Dlx5 and Msx2, respectively, based on their promoter activity modulation. Thus, the canonical BMP-2 signaling pathway plays a crucial part in the regulation of Dspp expression through the action of Smads, Dlx5, Runx2, and Msx2. Dentin sialophosphoprotein (DSPP)2 is a major non-collagenous dentin matrix protein and is mainly expressed by odontoblasts (1). DSPP is synthesized as a single polypeptide and then cleaved into three peptides, dentin sialoprotein (DSP), dentin glycoprotein (DGP), and dentin phosphoprotein (DPP) (2, 3). Evidence from human and mouse genetic studies indicates that DSPP is important for dentin mineralization (4); mutations of the DSPP gene have been identified in human families with dentinogenesis imperfecta II and III (5, 6), in whom dentin mineralization is defective. Moreover, Dspp-null mice show dentin mineralization defects that are very similar to human dentinogenesis imperfecta III.DSPP is a member of the small integrin-binding ligand N-linked glycoproteins (SIBLINGS) family of proteins, which also includes bone sialoprotein, osteopontin, dentin matrix protein 1, and matrix extracellular phosphoglycoprotein. The genes encoding these proteins are clustered on chromosome 4q21 in humans and 5q in mouse, and the proteins are commonly involved in dentin and bone mineralization and share an acidic serine-and aspartate-rich motif (7).The cleavage of DSPP into smaller proteins has been proposed to be an activation step (5). The failure of the cleavage process is a critical cause of defects in developmental dentin formation (3). DSP is in the N-te...

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Section: Discussionmentioning

confidence: 99%

The Canonical BMP Signaling Pathway Plays a Crucial Part in Stimulation of Dentin Sialophosphoprotein Expression by BMP-2

Cho

Yoon

Woo

et al. 2010

Journal of Biological Chemistry

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“…It has been reported that BMP-2 was detected at the apical and basal poles of preameloblasts in the developing mouse first lower molar [24], and, BMP-2, which induces ameloblast differentiation in vitro enamel organ culture [9]. These studies suggested that BMP-2 play a role on the ameloblasts differentiation.…”

Section: Discussionmentioning

confidence: 89%

Effect of BMP-2 on Gene Expression of Enamel Matrix Proteins at the Dental Epithelial Cell Line

Xu¹,

Takahashi²,

Harada³

et al. 2007

TOBIOTJ

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Epithelial-mesenchymal interactions play an important role in the control of ameloblasts and odentoblasts differentiation, and the bone morphogenetic proteins (BMPs) are known factors that regulate the differentiation of ameloblasts. We examined the effect of BMP-2 on the expression of the enamel matrix protein genes at the dental epithelial cell line. BMP-2 induced a 3-to 4-fold increase in amelogenin and ameloblastin mRNA expression, suggesting that BMP-2 is important for ameloblast differentiation. This finding has potential application in the tissue engineering of tooth re-constructions.

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“…Although previous studies documented several BMP subtypes (BMP2 to -7) expressed in the tooth germ (1), in particular, expression of BMP2 and BMP4 may be marked and associated with the epitheliummesenchyme interaction from the initiation stage to crown stage (1,15,17). Thus, we examined mRNA expression of BMP2 and BMP4 together with three BMP receptor subtypes (BMPR1a, 1b, and 2).…”

Section: Bmpmentioning

confidence: 99%

A systematic analysis for localization of predominant growth factors and their receptors involved in murine tooth germ differentiation using in situ hybridization technique

Hisamoto¹,

Goto²,

Muto³

et al. 2015

Biomed. Res.

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Tooth development is regulated by various growth factors and their receptors. However, the overall mechanism of growth factor-mediated odontogenesis remains to be elucidated. The present study examined expression sites and intensities of major growth factors and receptors in the tooth germ of murine fetuses and neonates. Signals of TGF-β and CTGF in fetuses were released from the enamel epithelium, while their neonatal signals arose in odontoblasts. Moreover, BMP/Smad signaling may affect the differentiation of ameloblasts, in contrast to PDGFα whose signals may cause odontoblast differentiation. Growth factors associated with the formation of the periodontium were IGF1, IGF2, IGFBP3, CTGF, and PDGFα. Concerning cusp formation, the enamel knot selectively expressed FGF4, BMP2, and BMP4 with an expression of PDGFα in the enamel-free area. It is concluded that many molecules play critical roles in the epithelium-mesenchyme interaction of tooth germ differentiation, and their expressions are precisely controlled.Tooth germ differentiation commonly progresses in the following order: the initiation, bud, cap, bell, and root formation stages. According to the stages, progenitor constituents of the tooth germ proliferate and are differentiated to form specialized parts of teeth and associated tissues. Tooth development is precisely regulated by cross-talk between adjacent tissues and various growth factors secreted in autocrine and paracrine modes. Recent studies in this research field have identified many molecules which play important roles in signaling associated with tooth germ differentiation, but it is largely unknown which growth factors are the main contributors to odontogenesis, partially due to insufficient in vivo systematic analyses of the expression of such factors. The transforming growth factor-β (TGF-β) superfamily may take a leading role in the regulation of cell proliferation, differentiation, and apoptosis, also being one of the major signals for tooth and periodontium morphogenesis. Immunohistochemical studies of the mouse tooth germ detected TGF-β1 in the inner enamel epithelium, ameloblasts, and odontoblasts; the expression of TGF-β receptor-1 (TGF-βR1) was weak in the enamel epithelium but increased in intensity in differentiated ameloblasts (6). An in situ hybridization study using mouse embryos identified an intense mRNA expression of TGF-β2/3 in the odontoblast layer (20). Among bone morphogenetic proteins (BMPs) which belong to the TGF-β family, it has been reported that the expression sites of BMP2 and BMP4 mRNA in the mouse tooth germ shift from the enamel knot to dental papilla and odontoblasts, and their signalings are required for the epithelium-mesenchyme interac-

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Immunolocalization of BMP-2/-4, FGF-4, and WNT10b in the Developing Mouse First Lower Molar

Cited by 70 publications

References 48 publications

The Canonical BMP Signaling Pathway Plays a Crucial Part in Stimulation of Dentin Sialophosphoprotein Expression by BMP-2

The Canonical BMP Signaling Pathway Plays a Crucial Part in Stimulation of Dentin Sialophosphoprotein Expression by BMP-2

Effect of BMP-2 on Gene Expression of Enamel Matrix Proteins at the Dental Epithelial Cell Line

<b>A systematic analysis for localization of predominant growth factors and their receptors involved in murine tooth germ differentiation using </b><i><b>in situ</b></i><b> hybridization </b><b>technique </b>

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