Cartilage matrix is composed of collagen II, which serves to provide this tissue with its high tensile strength, and the aggrecan proteoglycan which is mainly responsible for the reversible compressibility of cartilage. Collagen II expression changes during aging and during the pathogenesis of osteoarthritis. Work on this project focuses on studying the regulation of collagen II gene expression. The expression of this gene is dependent on sequences located both in the promoter region and in the first intron of the gene. A functional screening assay was used to identify proteins present in differentiated chondrocytes that can potentially activate collagen II transcription. Recently a polymorphism was described in a coding region of the human aggrecan gene. Preliminary studies suggest that there is an association between a specific allele of this gene and the occurrence of bilateral hand osteoarthritis in elderly white men in the BLSA study.