Bone morphogenetic proteins (BMPs) were discovered because they induce ectopic bone formation but now, on , Kamiya and colleagues unexpectedly report that BMP signalling negatively regulates bone mass during embryogenesis by upregulating the formation of bone-reabsorbing cells (osteoclasts). To investigate the role of BMP signalling during endogenous bone formation, the researchers disrupted the expression of the BMP receptor BMPR1A in osteoblasts (bone-forming cells) in mouse embryos. They show that levels of bone-resorption markers are reduced in these embryos(which indicates inhibition of osteoclastogenesis) and that bone mass is increased. Wnt signalling (which inhibits the RANKL-OPG pathway, an important mediator of osteoclastogenesis) is upregulated in the Bmpr1a-deficient osteoblasts, they report. Other experiments indicate that BMPR1A deficiency upregulates Wnt signalling by downregulating sclerostin, a Wnt inhibitor and bone mass mediator. Thus, the researchers suggest, BMP signalling in osteoblasts restrains endogenous bone mass indirectly by downregulating canonical Wnt signalling through sclerostin and,possibly, by directly upregulating the RANKL-OPG pathway.
