Bone Morphogenetic Protein-7 (Osteogenic Protein-1, OP-1) and Tooth Development

Abstract

Bone morphogenetic proteins (BMPs) form a family of growth factors originally isolated from extracellular bone matrix that are capable of inducing bone formation ectopically. We studied the expression, tissue localization, and function of BMP-7 (OP-1) during tooth development in rodents. Patterns of BMP-7 gene expression and peptide distribution indicated that BMP-7 was present in dental epithelium during the dental lamina, bud, and cap stages. During the bell stage, BMP-7 mRNA expression and protein distribution shifted from dental epithelium toward the dental mesenchyme. With advancing differentiation of odontoblasts, BMP-7 protein staining in the dental papilla became restricted to the layer of fully functional odontoblasts in the process of depositing (pre)dentin. Secretory-stage ameloblasts exhibited weak immunostaining for BMP-7. A restricted pattern of staining in ameloblasts became apparent in post-secretory stages of amelogenesis. Also, cells of the forming periodontal ligament were immunopositive. Histological analysis of tooth development in neonatal BMP-7-deficient mice did not reveal obvious changes compared with wild-type mice. We conclude that, in developing dental tissues, BMP-7 has distribution and expression patterns similar to those of other BMP members but is not an essential growth factor for tooth development, possibly because of functional redundancy with other BMP members or related growth factors.

Specific Amelogenin Gene Splice Products Have Signaling Effects on Cells in Culture and in Implants in Vivo

“…Conversely, the cells of the dental papilla could induce nonodontogenic epithelia to become committed to odontogenesis but only after the papilla cells had become odontogenic at EϾ12. Thus, signals instructive or permissive for differentiation pass between the two tissues at different developmental stages (2,54,58,59) during tooth morphogenesis. The elements of specificity that direct the programming of the differentiating cells remain undefined at this time.…”

Mechanical Loading Stimulates BMP7, But Not BMP2, Production by Osteocytes

“…Nonspecific binding sites were blocked by incubating tissue sections with normal goat serum (30%) for 30 min. Then, sections were incubated overnight at 4°C with primary antibodies to BMP2 [24] (1:50) and BMP7 [25] (1:100), kindly donated by Dr. J. Maliakal. Recombinant hBMP2 (COP-16, cloned in Escherichia coli) was used to raise the rabbit anti-BMP2 (rabbit 88) and recombinant hBMP7 (mature form, cloned in Chinese hamster ovary cells) to raise chicken anti-BMP7 (chicken 881).…”

Transgenic Overexpression of Gremlin Results in Developmental Defects in Enamel and Dentin in Mice

“…Detailed studies have mapped the temporospatial expression patterns of BMP-2,-4, and -7 during tooth development using the techniques of in situ hybridization and immunohistochemistry [8][9][10][11][12][13][14][15][16][17]. Briefly, at initiation of murine tooth development (E10-12), BMP-2 is expressed in the dental lamina, while BMP-4 is expressed in the epithelium and mesenchyme.…”

“…Briefly, at initiation of murine tooth development (E10-12), BMP-2 is expressed in the dental lamina, while BMP-4 is expressed in the epithelium and mesenchyme. As tooth development proceeds to the bud stage (E12-13), BMP-4 expression shifts completely to the mesenchyme, while BMP-2 and -7 are expressed in dental epithelium [8,11,16]. During the cap stage (E14-15), BMP-4 is expressed in the enamel knot, which is reported to be a signaling center regulating odontoblast differentiation [15], and in the dental mesenchyme.…”

“…At this time, expression of BMP-2 and -7 spreads from the enamel knot to the neighboring inner dental epithelium. At the bell stage (E16- 19), presumptive ameloblasts express BMP-4, and odontoblasts express BMP-2, -4, and -7 [8][9][10][11][12][13].…”