OSTEOARTHRITIS (OA) is a major cause of disability. The majority of clinically demonstrable secondary OA involves some compromise in joint stability. Rupture of the ANTERIOR CRUCIATE LIGAMENT (ACL) is a common SPORTS INJURY and OA frequently develops as a consequence. Elucidation of the molecular and cellular mechanisms in cartilage degeneration following ACL rupture would provide a rational approach towards management of this and other types of OA. Preliminary studies by the P.I. using the canine ACL model of OA established a marked increase in soluble TYPE VI COLLAGEN in the OA cartilage compared with controls.
The aims of the proposed study are to establish the quantities, molecular and fibrillar forms, tissue distribution, function and the control of synthesis of TYPE VI collagen in cartilage in the CANINE ACL- DEFICIENT MODEL. Quantitation of guanidine soluble Type VI collagen in articular cartilage of the animal model will be accomplished by ELISA assays. Immunoblotting of electrophoretic gels will establish the molecular forms and immunofluorescence and electron microscopy the tissue distribution and fibrillar forms of Type VI collagen. The function of Type VI collagen in cartilage will be investigated by measuring its ability to promote attachment of chondrocytes and to bind proteoglycans, Type II collagen and matrix glycoproteins from normal and experimental canine OA. The expression of Type VI collagen will be investigated in tissue explants and chondrocyte monolayer cultures of canine chondrocytes. An in vitro model of limited matrix degradation, accomplished by enzymatic and interleukin 1 mediated degradation of normal and experimental OA canine cartilage explants, will be employed to investigate the capacity of chondrocytes to synthesize Type VI and Type II collagens and proteoglycans in damaged matrices. The control of Type VI synthesis at the level of translation in normal and OA canine chondrocytes will be compared by analysis of in vitro translation products of chondrocyte mRNA.
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