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Recombinant human bone morphogenetic protein‐2 stimulates osteoblast differentiation and suppresses matrix metalloproteinase‐1 production in human bone cells isolated from mandibulae
Author(s) -
Takiguchi T.,
Kobayashi M.,
Suzuki R.,
Yamaguchi A.,
Isatsu K.,
Nishihara T.,
Nagumo M.,
Hasegawa K.
Publication year - 1998
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1111/j.1600-0765.1998.tb02347.x
Subject(s) - osteoblast , osteocalcin , endocrinology , medicine , bone morphogenetic protein 2 , parathyroid hormone , chemistry , alkaline phosphatase , bone morphogenetic protein , runx2 , biology , biochemistry , calcium , in vitro , enzyme , gene
Bone morphogenetic protein (BMP), a member of the transforming growth factor superfamily, is one of the most potent growth factors that stimulate osteoblast differentiation and bone formation. We investigated the effects of recombinant human BMP‐2 (rhBMP‐2) on osteoblast differentiation and matrix metalloproteinase‐1 (MMP‐1) production in human bone cells (HBC) isolated from mandibulae of 3 adult patients. rhBMP‐2 at concentrations over 50 ng/ml significantly stimulated alkaline phosphatase activity and parathyroid hormone (PTH)‐dependent 3′, 5′‐cyclic adenosine monophosphate accumulation, which are early markers of osteoblast differentiation, in HBCs. rhBMP‐2 (500 ng/ml) also enhanced the level of PTH/PTH related‐peptide receptor mRNA expression in HBCs. Although neither HBCs untreated nor treated with rhBMP‐2 produced measurable amounts of osteocalcin, which is a marker of more mature osteoblasts, 1,25‐dihydroxyvitamin D 3 [l,25(OH) 2 D 3 ] induced ostocalcin mRNA expression and its protein synthesis in these cells. rhBMP‐2 inhibited l,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 MMP‐1 mRNA expression at concentrations over 500 ng/ml. These results suggest that rhBMP‐2 exerts anabolic effects on human osteoblastic cells derived from mandibulae by stimulation of osteoblast differentiation and down‐regulation of MMP‐1 synthesis.