title: Regulation of osteogenic differentiation of human bone marrow stromal cells: interaction between transforming growth factor-beta and 1,25(OH)(2) vitamin D(3) In vitro.
abstract: 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-beta and its interaction with 1, 25(OH)(2) Vitamin D(3) [1,25(OH)(2)D(3)] on the differentiation and proliferation of human bone marrow stromal cells (hBMSC) in secondary cultures. Alkaline phosphatase (ALP) activity was inhibited by TGF-beta (0.1-10 ng/ml) and increased by 1, 25(OH)(2)D(3) (50 nM), however, co-treatment of TGF-beta and 1, 25(OH)(2)D(3) 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-beta alone, combined treatment with TGF-beta and 1, 25(OH)(2)D(3) had no effect on hBMSC proliferation. As no synergistic effect was seen with combinations of 1,25(OH)(2)D(3) 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-beta. The increased ALP activity was due to an enhancement of 1,25(OH)(2)D(3)-induced ALP activity by TGF-beta, rather than vice versa. In contrast, TGF-beta inhibited 1,25(OH)(2)D(3)-induced osteocalcin production. Taken together, these results indicate that TGF-beta and 1,25(OH)(2)D(3) act synergistically to stimulate the recruitment of BMSC to the osteoblast lineage. This interaction may play an important role in bone remodeling.
authors.affiliation: Human Metabolism and Clinical Biochemistry, Division of Biochemical and Musculoskeletal Medicine, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, Great Britain.
authors.forename: P
authors.initials: P
authors.lastname: Liu
authors.forename: B O
authors.initials: BO
authors.lastname: Oyajobi
authors.forename: R G
authors.initials: RG
authors.lastname: Russell
authors.forename: A
authors.initials: A
authors.lastname: Scutt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000096:biosynthesis; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D017154:Stromal Cells / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D016212:Transforming Growth Factor beta; D015675:Osteocalcin; D003907:Dexamethasone; D000469:Alkaline Phosphatase; D002117:Calcitriol