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 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 D3 [1,25(OH)2D3] induced ostocalcin mRNA expression and its protein synthesis in these cells. rhBMP-2 inhibited 1,25(OH)2D3-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.
Takiguchi
T
T
Department of Periodontics, Showa University Dental School, Tokyo, Japan.
Kobayashi
M
M
Suzuki
R
R
Yamaguchi
A
A
Isatsu
K
K
Nishihara
T
T
Nagumo
M
M
Hasegawa
K
K
D000328:Adult; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000096:biosynthesis; D000242:Cyclic AMP / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D008334:Mandible / Q000166:cytology; D020781:Matrix Metalloproteinase 1; D061965:Matrix Metalloproteinase Inhibitors; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology*; D015675:Osteocalcin / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D061965:Matrix Metalloproteinase Inhibitors; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D015675:Osteocalcin; D003094:Collagen; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; D017364:Collagenases; D020781:Matrix Metalloproteinase 1