GLUCOCORTICOID REGULATION OF TRANSFORMING GROWTH FACTOR-BETA-1 ACTIVITY AND BINDING IN OSTEOBLAST-ENRICHED CULTURES FROM FETAL-RAT BONE
GLUCOCORTICOID REGULATION OF TRANSFORMING GROWTH FACTOR-BETA-1 ACTIVITY AND BINDING IN OSTEOBLAST-ENRICHED CULTURES FROM FETAL-RAT BONE
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DOI：
10.1128/mcb.11.9.4490
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发表时间：
1991-09-01
影响因子：
5.3
通讯作者：
CANALIS, E
中科院分区：
文献类型：
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作者：
CENTRELLA, M;MCCARTHY, TL;CANALIS, E
转化生长因子β-（TGF-β）增强了复制和骨基质蛋白的合成，并与胎儿大鼠骨骼中成骨细胞富含成骨细胞的培养物中的不同结合位点相关。 在生物体中，高水平或持续暴露于糖皮质激素会改变骨细胞的活性并降低骨骼量，这可能部分是由于骨骼组织中局部TGF-beta-actions的变化所介导的。 成骨细胞添加的培养物对100 nm皮质醇的培养物降低了TGF-BETA-1对DNA和胶原蛋白合成的刺激作用，降低了40％至50％。 结合研究表明，皮质醇适度增强了总TGF-BETA-1结合，但是化学交联和聚丙烯酰胺凝胶电泳分析显示，仅在M（r）250,000（III型）TGF-Beta结合络合物中增加了增加，这被认为是据认为是表示细胞外TGF-beta存储位点。 相比之下，在M（R）65,000（I型）和85,000（II型）复合物中检测到TGF-BETA-1结合的降低，这些复合物已被视为信号诱导的TGF-beta受体。 因此，我们目前的研究表明，糖皮质激素可以降低骨骼中TGF-beta-1的合成代谢作用，并且这些作用可能部分是由于其与细胞外基质储存位点的结合重新分布而发生。 这种改变可能导致与糖皮质激素过量相关的骨质流失。
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 M(r) 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 M(r) 65,000 (type I) and 85,000 (type II) complexes, which have been implicated as signal-tranducing 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.