Modulation of biosynthetic patterns of human articular chondrocytes by cytokines and growth factors - quantitative evaluation at the mRNA levels

The modulation of biosynthetic patterns of human articular chondrocytes by cytokines and growth factors was investigated in vitro by analysing the gene expression of cartilage matrix components at the mRNA level. The effects of IL-1$ beta$, TGF-$ beta$, and IGF-1, individually or in combination on expression of mRNAs for type II collagen, aggrecan, stromelysin, collagenase, and tissue inhibitor of metalloproteinases (TIMP) were quantitatively determined by competitive PCR. The results revealed that each of these mRNA species had an unique response pattern to these external agents. TGF-$ beta$ enhanced expression of mRNAs for type II collagen, aggrecan, and TIMP, while it depressed the expression of metalloproteinases. In contrast, IL-1 regulated expression of these mRNAs in an opposite fashion. The magnitude of response to IL-1 and TGF-$ beta$ varies for different target mRNAs. A prolonged incubation with TGF-$ beta$ effectively reversed the IL-1-induced depression of TIMP-1 mRNA level. IGF-1 increased the mRNA levels for aggrecan and type II collagen, and effectively reversed the inhibitory effects of IL-1 on these two genes. This study indicates how physiologically-relevant cytokines and growth factors regulate the expression of structural and degradative components by articular chondrocytes. The understanding of the factors regulating the biosynthetic behaviors of articular chondrocytes under various physiological and pathological conditions is important if effective repair of the tissue is to be achieved