Recombinant human bone morphogenetic protein-2 stimulates osteoblast differentiation and suppresses matrix metalloproteinase-1 production in human bone cells isolated from mandibulae

Bone morphogenetic protein (BMP), a member of the transforming growth facto r superfamily, is one of the most potent growth factors that stimulate oste oblast differentiation and bone formation. We investigated the effects of r ecombinant human BMP-2 (rhBMP-2) on osteoblast differentiation and matrix m etalloproteinase-1 (MMP-1) production in human bone cells (HBC) isolated fr om mandibulae of 3 adult patients, rhBMP-2 at concentrations over 50 ng/ml significantly stimulated alkaline phosphatase activity and parathyroid horm one (PTH)-dependent 3', 5'-cyclic adenosine monophosphate accumulation, whi ch are early markers of osteoblast differentiation, in HBCs. rhBMP-2 (500 n g/ml) also enhanced the level of PTH/PTH related-peptide receptor mRNA expr ession in HBCs. Although neither HBCs untreated nor treated with rhBMP-2 pr oduced measurable amounts of osteocalcin, which is a marker of more mature osteoblasts, 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] induced ostocalcin mRNA expression and its protein synthesis in these cells, rhBMP-2 inhibited 1,25(OH)(2)D-3-induced osteocalcin synthesis in HBCs at both the mRNA and protein level. rhBMP-2 also significantly suppressed MMP-1 production and M MP-1 mRNA expression at concentrations over 500 ng/ml. These results sugges t that rhBMP-2 exerts anabolic effects on human osteoblastic cells derived from mandibulae by stimulation of osteoblast differentiation and downregula tion of MMP-1 synthesis.