Extracellular collagen regulates expression of transforming growth factor-beta 1 gene

A complex interrelationship exists between the extracellular matrix and cyt okine signaling in articular chondrocytes. We sought to determine whether t he extracellular matrix serves as a regulatory component of transforming gr owth factor-beta1 expression. Bovine articular chondrocytes were isolated a nd resuspended in alginate, yielding final extracellular protein concentrat ions of 0 to 1.5% (wt/vol) for type-II or type-I collagen. Cultures were ma intained for 7 days in the presence or absence of transforming growth facto r-beta1-supplemented medium (10 ng/ml). The amount of transforming growth f actor-beta1 mRNA was examined with quantitative competitive reverse transcr iption-polymerase chain reaction analysis. The results indicate that exogen ous transforming growth factor-beta1 stimulates endogenous transforming gro wth factor-beta1 mRNA expression approximately 8-fold. This effect depended on the concentration of extracellular type-II collagen. As the concentrati on of extracellular type-II collagen is increased, the expression of transf orming growth factor-beta1 mRNA decreases in both basal and transforming gr owth factor-beta1-stimulated cultures. Exogenous extracellular type-I colla gen also served to negatively modulate transforming growth factor-beta1 gen e expression but with a different concentration profile. The results demons trate that transforming growth factor-beta1 mRNA expression was upregulated by exogenous transforming growth factor-beta1 and was downregulated by ext racellular type-I and type-II collagens. The profoundly different effects o n transforming growth factor-beta1 expression by the two collagens are cons istent with those reported for mammary epithelial cells and likely serve as a negative feedback mechanism to preserve tissue homeostasis.