Secretion of Chondrocyte Stimulating Factor by Macrophages As a Result of Activation with Collagen and Proteoglycans

In this study, we have investigated the role of extracellular matrix components of connective tissue, collagen and proteoglycans, in the activation of rabbit macrophages and articular chondrocytes. Addition of type II collagen, in native or denatured form, or proteoglycan subunits, led to the activation of macrophages and release of chondrocyte stimulating factor. Type I collagen, when used at higher concentrations, was also capable of macrophage activation. The conditioned media of activated macrophages induced an increased protease synthesis by chondrocytes. Collagen or proteoglycan subunits did not have any direct stimulatory effect on chondrocytes. Intraperitoneal injections of collagen induced infiltration of macrophages into the peritoneal cavity. Although these macrophages failed to produce significant levels of chondrocyte stimulating factor by themselves, they could be activated in culture with lipopolysaccharides or collagen to produce chondrocyte stimulating factor. The chondrocytes, treated with the conditioned medium of activated macrophages (with lipopolysaccharides or cartilage matrix components), failed to survive in suspension cultures.