Villiger P M, Lotz M
Sam and Rose Stein Institute for Research on Aging, University of California San Diego, La Jolla 92093.
J Cell Physiol. 1992 May;151(2):318-25. doi: 10.1002/jcp.1041510213.
Transforming growth factor beta (TGF beta) is a family of important regulators of chondrocyte growth and differentiation. Although TGF beta has been detected in cartilage, the TGF beta isoforms expressed by chondrocytes and their regulation by growth factors are unknown. This study shows that human articular chondrocytes release TGF beta activity. Chondrocyte conditioned media contains active TGF beta and larger quantities in latent form. By neutralization with specific antibodies it is shown that all three isoforms (TGF beta 1, TGF beta 2, and TGF beta 3) are secreted by chondrocytes. Analysis of the inducers of TGF beta gene expression demonstrates complex regulation of TGF beta production by growth factors. Basic fibroblast growth factor (bFGF) stimulates the release of TGF beta activity but has no effect on steady state TGF beta mRNA levels while platelet-derived growth factor (PDGF) upregulates TGF beta 1 and TGF beta 3 mRNAs with a corresponding increase in protein secretion. The three TGF beta isoforms themselves differentially affect gene expression. While TGF beta 1 and TGF beta 2 show autoinduction, TGF beta 3 upregulates TGF beta 1 but does not affect TGF beta 2 mRNA levels. These results demonstrate that human articular chondrocytes produce all three TGF beta isoforms. Induction of TGF beta expression is differentially regulated by various growth factors and occurs at the mRNA level and/or posttranscriptionally. Chondrocyte expression and the differential regulation of TGF beta 1, TGF beta 2, and TGF beta 3 by growth factors suggest that all three isoforms of TGF beta are part of the network of cartilage regulatory factors.
转化生长因子β（TGF-β）是软骨细胞生长和分化的重要调节因子家族。尽管在软骨中已检测到TGF-β，但软骨细胞表达的TGF-β亚型及其受生长因子的调节情况尚不清楚。本研究表明，人关节软骨细胞可释放TGF-β活性。软骨细胞条件培养基含有活性TGF-β以及大量潜伏形式的TGF-β。通过用特异性抗体中和表明，软骨细胞分泌所有三种亚型（TGF-β1、TGF-β2和TGF-β3）。对TGF-β基因表达诱导剂的分析表明，生长因子对TGF-β的产生具有复杂的调节作用。碱性成纤维细胞生长因子（bFGF）刺激TGF-β活性的释放，但对稳态TGF-βmRNA水平无影响，而血小板衍生生长因子（PDGF）上调TGF-β1和TGF-β3的mRNA，并相应增加蛋白质分泌。三种TGF-β亚型本身对基因表达有不同影响。虽然TGF-β1和TGF-β2显示出自身诱导作用，但TGF-β3上调TGF-β1但不影响TGF-β2的mRNA水平。这些结果表明，人关节软骨细胞可产生所有三种TGF-β亚型。TGF-β表达的诱导受多种生长因子的差异调节，且发生在mRNA水平和/或转录后水平。软骨细胞对TGF-β1、TGF-β2和TGF-β3的表达及生长因子的差异调节表明这三种TGF-β亚型都是软骨调节因子网络的一部分。
