Recombinant human bone morphogenetic protein-2 stimulates osteoblast differentiation and suppresses matrix metalloproteinase-1 production in human bone cells isolated from mandibulae
T. Takiguchi et al., Recombinant human bone morphogenetic protein-2 stimulates osteoblast differentiation and suppresses matrix metalloproteinase-1 production in human bone cells isolated from mandibulae, J PERIOD RE, 33(8), 1998, pp. 476-485
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.