Regulation of osteogenic differentiation of human bone marrow stromal cells:: Interaction between transforming growth factor-β and 1,25(OH)2 vitamin D3 in vitro
Regulation of osteogenic differentiation of human bone marrow stromal cells:: Interaction between transforming growth factor-β and 1,25(OH)2 vitamin D3 in vitro
复制标题
DOI：
10.1007/s002239900678
复制
发表时间：
1999-08-01
影响因子：
4.2
通讯作者：
Scutt, A
中科院分区：
文献类型：
--
作者：
Liu, P;Oyajobi, BO;Scutt, A
骨髓基质细胞被认为在骨形成中起着重要作用，作为骨祖细胞的主要来源，然而，关于这些细胞的成骨分化如何受全身激素和局部生长因子的调节知之甚少。我们研究了TGF-β及其与1，25（OH）（2）维生素D-3 [1，25（OH）（2）D-3]的相互作用对人骨髓基质细胞（hBMSC）分化和增殖的影响。碱性磷酸酶（ALP）活性被TGF-β（0.1-10 ng/ml）抑制，并被1，25（OH）（2）D-3（50 nM）增加，然而，TGF-β和1，25（OH）（2）D-3的共同处理协同增强ALP活性，最大刺激发生在处理后约8天。这种协同效应与增殖无关，因为与单独的TGF-β相比，TGF-β和1，25（OH）（2）D-3的联合处理对hBMSC增殖没有影响。由于1，25（OH）（2）D-3与其他骨营养生长因子（包括BMP-2、IGF-I和碱性成纤维细胞生长因子（bFGF））的组合未观察到协同效应，因此似乎协同相互作用对TGF-β具有特异性。ALP活性的增加是由于TGF-β增强了1，25（OH）（2）D-3诱导的ALP活性，而不是相反。相反，TGF-β抑制1，25（OH）（2）D-3诱导的骨钙素产生。总之，这些结果表明，TGF-β和1，25（OH）（2）D-3协同作用，刺激BMSC向成骨细胞谱系的募集。这种相互作用可能在骨重建中起重要作用。
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.