The Identification of Degradative Products in Type VI Collagen after Stimulation with Catabolic Agents, Pro-Inflammatory Interleukin-1beta (IL-1beta) and all-Trans Retinoic Acid (RA) in Articular Cartilage. Articular cartilage destruction is a major feature of osteoarthritis which develops after traumatic sports injury. Individuals who participate in sports experience minor or overt injuries to the knee articular cartilage and this may lead to osteoarthritis (OA). In articular cartilage, the matrix glycoprotein type VI collagen is a major component of the pericellular matrix surrounding chondrocytes. Type VI collagen binds to receptors on the chondrocytes cell surface and to extracellular matrix ligands. In this way, the pericellular environment of the chondrocytes plays a critical role in cell matrix interactions to maintain homeostasis and repair in injured tissue. Any degradation of the type VI collagen, therefore, could lead to miscommunication between the cell and its matrix. The goal of this application is to identify the degradation products of Type VI collagen after incubation of bovine articular cartilage and meniscus cartilage with interleukin-1beta (IL- 1beta) and retinoic acid (RA) in vitro. The tissue will be extracted and its degradation products identified by Western blotting detection using anti-type VI collagen monoclonal antibodies. This project will be the first to identify the cellular degradation products of type VI collagen. Establishing how the type VI collagen molecule is degraded would be an important first step toward understanding the cascade in cartilage destruction. The specific stimuli responsible for type VI degradation have not yet been defined. The suggested evidence in this proposal will possibly provide the very first evidence in identifying the specific role of proteolytic cleavage in type VI collagen. With this knowledge, a rational approach will be provided for developing potential diagnostic therapy aimed at reducing or stopping the degradation of cartilage, especially in osteoarthritis and sports related injuries.
