BMP Receptor1A Determines the Fate of Dentin, Cementum and Bone

OBJECTIVES: Odontoblasts, cementoblasts, periodontal ligament cells or osteoblasts are originated from mesenchymal cells. Molecule (s) that determines the fate of the precursors towards bone or tooth is largely unknown in vivo. As deletion of the Bmpr1a receptor results in embryonic lethality, prior to bone and tooth formation, our goal was to determine the role of the BMP receptor 1A (Bmpr1a) in early bone and tooth development by tissue-specific and stage-specific knockout approaches. METHODS: To delete the Bmpr1a gene specifically in progenitors for bone and tooth, the 2.3 kb or 3.6 kb Col 1a1-cre (active in odontoblasts, cementoblasts, osteoblasts, and periodontal ligament cells), or the 3.2 kb ERt2-Cre (a tamoxifen inducible Cre) mice were crossed to floxed Bmpr1a mice. Bone and teeth from the Bmpr1a conditional knockout (cKO) mice were characterized using histology, radiography, SEM, and gene-chips. RESULTS: The cKO Bmpr1a mice displayed the following abnormalities: a) extremely thin dentin with fewer odontoblasts which were no longer polarized; b) bone-like osteoid filled in the tooth pulps with osteocyte-like cells embed in dentin; c) acellular and cellular layers of cementum were absent; d) the PDL was hypoplastic and replaced by loosely disorganized fibers; e) ectopic bone callus is formed in response to dentin fracture instead of normal secondary dentin; f) mineral density was dramatically reduced in dentin and bone; and g) expression levels of genes linked to craniofacial and tooth development, such as TGFb3, DKK3 and LTBP2 were reduced. CONCLUSION: BMPR1A directs differentiation of mesenchymal precursors into cementoblasts, odontoblasts, and PDL cells, but blocks osteogenesis. Work supported by NIH/NIDCR T32DE07294, DE00455, and AR51587.