Effects of BMP-2 on osteoblastic cells and on skeletal growth and bone formation in unloaded rats.
A previous study showed that skeletal unloading induced by hindlimb suspension for 14 days in rats reduces osteoblastic cell proliferation, inhibits skeletal growth and bone formation and induces metaphyseal bone loss. This study investigated the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) in this model. In vitro analysis showed that rhBMP-2 (25-100 ng/ml, 48-96 h) increased alkaline phosphatase activity, an early marker of osteoblast differentiation, in rat neonatal calvaria cells and adult marrow stromal cells, showing that rhBMP-2 induced the differentiation of osteoblast precursor cells in vitro. In contrast, rhBMP-2 did not increase rat calvaria or marrow stromal cell proliferation. Biochemical and histomorphometric analysis showed that systemic infusion with rhBMP-2 (2 microg/kg/day) in unloaded rats had no significant effect on serum osteocalcin levels and on histomorphometric indices of bone formation. Accordingly, rhBMP-2 infusion did not prevent the decreased skeletal growth, trabecular bone bone volume and bone mineral content induced by unloading. The present data indicate that, although rhBMP-2 stimulates osteoblastic cell differentiation, rhBMP-2 infusion is not effective in increasing bone formation and in preventing trabecular bone loss induced by unloading in rats.
Zerath
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E
IMASSA-CERMA, Department of Gravitational Physiology, Brétigny sur Orge, France.
Holy
X
X
Noël
B
B
Malouvier
A
A
Hott
M
M
Marie
P J
PJ
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D001851:Bone Diseases, Metabolic / Q000473:pathology; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005269:Femur / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D015675:Osteocalcin / Q000097:blood; D051381:Rats; D011994:Recombinant Proteins; D012886:Skull / Q000166:cytology / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects; D013977:Tibia / Q000187:drug effects / Q000254:growth & development; D016212:Transforming Growth Factor beta
C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D015675:Osteocalcin; D000469:Alkaline Phosphatase