Differential effects of transforming growth factor beta2, dexamethasone and 1,25-dihydroxyvitamin D on human bone marrow stromal cells.
We have studied the effects of rhTGF-beta2, dexamethanosome (dex) and 1,25(OH)2D3 on human bone marrow stromal (HBMS) cells in long-term culture. A fraction on HBMS expressed type I collagen (Col I) and osteopontin, and transient treatment (48 h) with dex increased the number of alkaline phosphatase (ALP) positive cells. Treatment with rhTGF-beta2 inhibited DNA synthesis and attenuated the stimulatory effect of dex on cell growth at 3-4 weeks of culture. 1,25(OH)2D3 inhibited DNA synthesis at 1-4 weeks, and dex partially blocked the inhibitory effect of 1,25(OH)2D3 on cell growth. rhTGF-beta2 and dex increased Col I synthesis at 1 week of culture. Both dex and 1,25(OH)2D3 increased ALP activity and mRNA levels independently, and when combined they had an additive or synergistic effect, whereas rhTGF-beta2 antagonized the stimulatory effect of dex on ALP activity. In addition, dex attenuated the increased osteocalcin expression induced by 1,25(OH)2D3. These results show that rhTGF-beta2, dex and 1,25(OH)2D3 have distinct effects and modulate the action of each other on human marrow stromal cell proliferation and differentiation at different time points during the culture.
Fromigué
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INSERM Unit 349, Cell and Molecular Biology of Bone Cartilage, Lariboisière Hospital, Paris, 75475, France.
Marie
P J
PJ
Lomri
A
A
D000368:Aged; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D002113:Calcification, Physiologic; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D004247:DNA / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D015675:Osteocalcin / Q000096:biosynthesis / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D011994:Recombinant Proteins / Q000494:pharmacology; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D015675:Osteocalcin; D003907:Dexamethasone; D003094:Collagen; D004247:DNA; D000469:Alkaline Phosphatase; D002117:Calcitriol