Restoration of the Extracellular Matrix in Human Osteoarthritic Articular Cartilage by Overexpression of the Transcription Factor SOX9

terized by a pathologic shift in articular cartilage ho-meostasis toward the progressive loss of extracellular matrix (ECM). The purpose of this study was to inves-tigate the ability of rAAV-mediated SOX9 overexpres-sion to restore major ECM components in human OA articular cartilage. Methods. We monitored the synthesis and content of proteoglycans and type II collagen in 3-dimensional cultures of human normal and OA articular chondro-cytes and in explant cultures of human normal and OA articular cartilage following direct application of a recombinant adeno-associated virus (rAAV) SOX9 vec-tor in vitro and in situ. We also analyzed the effects of this treatment on cell proliferation in these systems. Results. Following SOX9 gene transfer, expressio