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.