Essential requirement of BMPs-2/4 for both osteoblast and osteoclast formation in murine bone marrow cultures from adult mice: Antagonism by noggin

Bone morphogenetic proteins (BMPs) have been heretofore implicated in the i nduction of osteoblast differentiation from uncommitted progenitors during embryonic skeletogenesis and fracture healing. We have tested the hypothesi s that BMPs are also involved in the osteoblastogenesis that takes place in the bone marrow in postnatal life. To do this, we took advantage of the pr operties of noggin, a recently discovered protein that binds BMP-2 and -4 a nd blocks their action. Addition of human recombinant noggin to bone marrow cell cultures from normal adult mice inhibited both osteoblast and osteocl ast formation; these effects were reversed by exogenous BMP-2. Consistent w ith these findings, BMP-2 and -4 and BMP-2/4 receptor transcripts and prote ins were detected in these primary cultures, in a bone marrow-derived strom al/osteoblastic cell line, as well as in murine adult whole bone; noggin ex pression was also documented in all these preparations. Moreover, addition of antinoggin antibody caused an increase in osteoblast progenitor formatio n. These findings suggest that BMP-2 and -4 are expressed in the bone marro w in postnatal life and serve to maintain the continuous supply of osteobla sts and osteoclasts; and that, in fact, BMP-2/4-induced commitment to the o steoblastic lineage is a prerequisite for osteoclast development. Hence, BM Ps, perhaps in balance with noggin and possibly other antagonists, may prov ide the tonic baseline control of the rate of bone remodeling on which othe r inputs (e.g., hormonal, biomechanical, etc.) operate.