Cartilage is a unique tissue that functions to cushion the impact between bones and is a target for degenerative changes that result in osteoarthritis (OA), an incurable disease that afflicts millions of elderly individuals. OA involves changes in expression of matrix proteins such as collagen II, the death of the only cell type in cartilage-the chondrocyte, and overexpression of specific matrix metalloproteases (MMPs) that contribute to the breakdown of the cartilage matrix. We are continuing to characterize transcriptional regulatory sequences in the collagen II gene. In addition to the intron enhancer, we have identified a region of the promoter that appears to be required for activation of transcription. This region contains putative binding sites for both SP-1 and bHLH transcription factors. We have made significant progress in studying the potential for cell-based cartilage repair. To date we have shown conclusively that adult rabbit articular chondrocytes can be phenotypically modulated and expanded in vitro with growth factors. Importantly, these cells retain the capacity to form hyaline cartilage when reintroduced into animals. Preliminary work suggests that a similar approach may prove feasible with human chondrocytes. Finally, we have shown that an immortalized chondrocyte line developed in our laboratory displays a similar pattern of MMP expression upon cytokine stimulation as has been described in human OA. These studies may lead to novel therapeutic approaches for OA.
