STIMULATORY EFFECT OF BONE MORPHOGENETIC PROTEIN-2 ON OSTEOCLAST-LIKECELL-FORMATION AND BONE-RESORBING ACTIVITY

Although the action of bone morphogenetic protein (BMP) on osteoblast differentiation has been extensively investigated, its effect on osteo clast differentiation remains unknown. In the present study, in vitro effects of BMP-2 on osteoclast-like cell formation and bone resorption ,were examined. BMP-2 (1-100 ng/ml) significantly stimulated bone reso rption by preexistent osteoclast-like cells in mouse bone cell culture s containing stromal cells, whereas it did not affect the bone-resorbi ng activity of isolated rabbit osteoclast-like cells. When BMP-2 was a dded to unfractionated bone cells after degeneration of preexistent os teoclast-like cells, BMP-2, dose-dependently stimulated osteoclast-lik e cell formation at a minimal effective concentration of 10 pg/ml. BMP -2 also enhanced the osteoclast-like cell formation induced by 1,25-di hydroxyvitamin D-3 (1,25(OH)(2)D-3). Moreover, osteoclast-like cells n ewly formed by BMP-2 from unfractionated bone cells possessed the abil ity to form pits on dentine slices, Because these results indicated th at BMP-2 directly or indirectly stimulated osteoclast differentiation and activity, we next examined the direct effect of BMP-2 on osteoclas t precursors in the absence of stromal cells using hemopoietic blast c ells derived from spleen cells. The mRNA for BMP-2/4 receptor was dete cted in hemopoietic blast cells supported by granulocyte-macrophage co lony-stimulating factor (GM-CSF) as well as osteoblastic MC3T3-E1 cell s and MC3T3-G2/PA6 stromal cells by RNase protection assay, BMP-2 dose -dependently stimulated osteoclast-like cell formation from hemopoieti c blast cells supported by GM-CSF at a minimal effective concentration of 10 pg/ml. BMP-2 also enhanced 1,25(OH)(2)D-3-induced osteoclast-li ke cell formation from hemopoietic blast cells. The present data are t he first to indicate that BMP-2 stimulates bone resorption through bot h direct stimulation of osteoclast formation and activation of mature osteoclasts, possibly via stromal cells, in vitro.