Method: A mouse model that is null for expression of the BMPRII in osteoclasts was generated by mating floxed BMPRII mice with mice that express cre recombinase in the myeloid cell lineage. Efficient deletion of Bmpr2 was verified by real time RT-PCR. We examined M-CSF and RANKL mediated osteoclast formation and gene expression in primary bone marrow derived precursors from the BMPRII conditional knock out mice. Regulation of BMP signaling was confirmed by examining pSmad1/5/8, p38, and pERK levels. Effects of BMPRII-deletion on osteoclast formation were examined by quantitation of multinucleated TRAP-positive cells. Expression of osteoclast differentiation and fusion genes was examined by real-time RT-PCR.
Result: Micro-CT analysis of BMPRII-LysM Cre showed increased trabecular bone at 3 and 6 months compared to WT. Osteoclasts from BMPRII-LysM Cre bone marrow monocyte (BMM) cultures were smaller than controls, and showed reduced expression of key genes involved in osteoclastogenesis including NFATc1, cathepsin K, OC-STAMP and Acp5.
Conclusion: These results show that BMPs are required for osteoclastogenesis in vivo. Investigating the mechanism(s) by which BMPs control osteoclast function will improve our understanding of physiological regulation of bone remodeling and pathogenesis of diseases that result from altered bone remodeling, as well as the understanding of the therapeutic efficacy of BMP-induced bone regenerative protocols.
(NIH/NIDCR: T32DE007288 and T90DE022732 (L.D.P.); R01AR056642 (R.G.))