Centrella M, McCarthy T L, Canalis E
Department of Research, Saint Francis Hospital and Medical Center, Hartford, Connecticut 06105.
Mol Cell Biol. 1991 Sep;11(9):4490-6. doi: 10.1128/mcb.11.9.4490-4496.1991.
Transforming growth factor beta (TGF-beta) enhances replication and bone matrix protein synthesis and associates with distinct binding sites in osteoblast-enriched cultures from fetal rat bone. In the organism high levels of or sustained exposure to glucocorticoids alters bone cell activity and decreases bone mass, effects that may be mediated in part by changes in local TGF-beta actions in skeletal tissue. Preexposure of osteoblast-enriched cultures to 100 nM cortisol reduced the stimulatory effects of TGF-beta 1 on DNA and collagen synthesis by 40 to 50%. Binding studies showed that cortisol moderately enhanced total TGF-beta 1 binding, but chemical cross-linking and polyacrylamide gel electrophoretic analysis revealed an increase only within Mr 250,000 (type III) TGF-beta-binding complexes, which are thought to represent extracellular TGF-beta storage sites. In contrast, a decrease in TGF-beta 1 binding was detected in Mr 65,000 (type I) and 85,000 (type II) complexes, which have been implicated as signal-transducing TGF-beta receptors. Our present studies therefore indicate that glucocorticoids can decrease the anabolic effects of TGF-beta 1 in bone, and these may occur in part by a redistribution of its binding toward extracellular matrix storage sites. Alterations of this sort could contribute to bone loss associated with glucocorticoid excess.
转化生长因子β（TGF-β）可增强复制和骨基质蛋白合成，并与来自胎鼠骨的富含成骨细胞的培养物中的不同结合位点相关联。在生物体内，高水平的糖皮质激素或持续暴露于糖皮质激素会改变骨细胞活性并降低骨量，这些作用可能部分是由骨骼组织中局部TGF-β作用的变化介导的。将富含成骨细胞的培养物预先暴露于100 nM皮质醇可使TGF-β1对DNA和胶原蛋白合成的刺激作用降低40%至50%。结合研究表明，皮质醇适度增强了总TGF-β1结合，但化学交联和聚丙烯酰胺凝胶电泳分析显示仅在分子量250,000（III型）的TGF-β结合复合物中增加，这些复合物被认为代表细胞外TGF-β储存位点。相比之下，在分子量65,000（I型）和85,000（II型）的复合物中检测到TGF-β1结合减少，这些复合物被认为是信号转导TGF-β受体。因此，我们目前的研究表明，糖皮质激素可降低TGF-β1在骨中的合成代谢作用，并且这些作用可能部分是通过其结合向细胞外基质储存位点的重新分布而发生的。这种改变可能导致与糖皮质激素过量相关的骨质流失。
