Human BMP-7/OP-1 induces the growth and differentiation of adipocytes and osteoblasts in bone marrow stromal cell cultures.
We studied the effects of BMP-7/OP-1 on growth and differentiation of bone marrow stromal cells. BMS2, a mouse bone marrow stromal cell line capable of differentiating into adipocytes and osteoblasts, were treated in a serum-free medium containing differentiation agents that favor the expression of both lineages. BMP-7/OP-1 stimulated cell proliferation and differentiation concomitantly. These effects were dose- and growth phase-dependent. Cells were more sensitive to the treatment early in the culture (30-40% confluence) with a significant increase in cell proliferation and markers of differentiation at low concentrations. When treated later in the growth phase (90-100% confluence), no significant increase in cell proliferation was seen. The concentration requirement for cells later in the culture to reach an equivalent degree of differentiation was 3-10- fold higher than for cells treated early. In both cases, the effects on adipocyte differentiation were biphasic; low concentrations stimulated adipocyte differentiation which was inhibited at higher concentrations where stimulation of osteoblast markers were observed. We conclude that cell proliferation and cell differentiation into adipocyte/osteoblast can occur simultaneously under BMP-7/OP-1 treatment.
Chen
T L
TL
Department of Natural Sciences, College of Notre Dame, Belmont, California 94002, USA. tlcbio@cnd.edu
Shen
W J
WJ
Kraemer
F B
FB
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D000469:Alkaline Phosphatase / Q000096:biosynthesis / Q000235:genetics; D000818:Animals; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D011416:Complement Factor D; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D015675:Osteocalcin / Q000032:analysis; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics; D002787:Sterol Esterase / Q000096:biosynthesis / Q000235:genetics; D013268:Stimulation, Chemical; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects; D016212:Transforming Growth Factor beta
C525819:BMP7 protein, human; D015415:Biomarkers; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D020033:Protein Isoforms; D016212:Transforming Growth Factor beta; D015675:Osteocalcin; D003094:Collagen; D002787:Sterol Esterase; D000469:Alkaline Phosphatase; D012697:Serine Endopeptidases; C493488:CFD protein, human; D011416:Complement Factor D; C493491:complement factor D, mouse; D006854:Hydrocortisone; D007213:Indomethacin