Bone marrow stromal cells are believed to play a major role in bone formation as a major source of osteoprogenitor cells, however, very little is known about how the osteogenic differentiation of these cells is regulated by systemic hormones and local growth factors. We examined the effects of TGF- β and its interaction with 1,25(OH)2 Vitamin D3 [1,25(OH)2D3] on the differentiation and proliferation of human bone marrow stromal cells (hBMSC) in secondary cultures. Alkaline phosphatase (ALP) activity was inhibited by TGF-β (0.1-10 ng/ml) and increased by 1,25(OH)2D3 (50 nM), however, co- treatment of TGF-β and 1,25(OH)2D3 synergistically enhanced ALP activity with maximal stimulation occurring at about 8 days after treatment. This synergistic effect was independent of proliferation because, in contrast to TGF-β alone, combined treatment with TGF-β and 1,25(OH)2D3 had no effect on hBMSC proliferation. As no synergistic effect was seen with combinations of 1,25(OH)2D3 and other osteotrophic growth factors, including BMP-2, IGF- I, and basic fibroblast growth factor (bFGF), it would seem likely that the synergistic interaction is specific for TGF-β. The increased ALP activity was due to an enhancement of 1,25(OH)2D3-induced ALP activity by TGF-β, rather than vice versa. In contrast, TGF-β inhibited 1,25(OH)2D3-induced osteocalcin production. Taken together, these results indicate that TGF-β and 1,25(OH)2D3 act synergistically to stimulate the recruitment of BMSC to the osteoblast lineage. This interaction may play an important role in bone remodeling.
- Human bone marrow stromal cells
- Osteogenic differentiation
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Orthopedics and Sports Medicine