Liu P, Oyajobi B O, Russell R G, Scutt A
Human Metabolism and Clinical Biochemistry, Division of Biochemical and Musculoskeletal Medicine, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, Great Britain.
Calcif Tissue Int. 1999 Aug;65(2):173-80. doi: 10.1007/s002239900678.
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.
骨髓基质细胞被认为作为骨祖细胞的主要来源，在骨形成中发挥主要作用，然而，对于这些细胞的成骨分化如何受到全身激素和局部生长因子的调节却知之甚少。我们研究了转化生长因子-β（TGF-β）及其与1,25-二羟维生素D3[1,25(OH)2D3]的相互作用对人骨髓基质细胞（hBMSC）传代培养时分化和增殖的影响。碱性磷酸酶（ALP）活性受到TGF-β（0.1-10 ng/ml）的抑制，并被1,25(OH)2D3（50 nM）增强，然而，TGF-β和1,25(OH)2D3共同处理可协同增强ALP活性，最大刺激作用出现在处理后约8天。这种协同作用与增殖无关，因为与单独使用TGF-β相比，TGF-β和1,25(OH)2D3联合处理对hBMSC增殖没有影响。由于1,25(OH)2D3与其他骨营养生长因子（包括骨形态发生蛋白-2、胰岛素样生长因子-I和碱性成纤维细胞生长因子（bFGF））联合使用时未观察到协同作用，因此这种协同相互作用似乎对TGF-β具有特异性。ALP活性的增加是由于TGF-β增强了1,25(OH)2D3诱导的ALP活性，而不是相反。相反，TGF-β抑制1,25(OH)2D3诱导的骨钙素产生。综上所述，这些结果表明TGF-β和1,25(OH)2D3协同作用以刺激骨髓间充质干细胞向成骨细胞谱系的募集。这种相互作用可能在骨重塑中起重要作用。
