Future directions for research and treatment of osteoarthritis.

Future directions in the research and treatment of osteoarthritis (OA) will be based on the emerging picture of pathophysiological events that govern the initiation and progression of OA. The fundamental event resulting in the destruction of articular cartilage in OA arises from an imbalance between anabolic and catabolic pathways. The extracellular matrix (ECM) of cartilage is degraded by matrix metalloproteinases (MMPs) induced by cytokines. Cytokines also blunt chondrocyte compensatory synthesis pathways required to restore the integrity of the degraded ECM. Inhibition of the MMPs, their activators, and cytokines that induce MMP gene up-regulation would appear to be fertile targets for drug development in the treatment of OA. Restoration of damaged articular surfaces via tissue engineering strategies which could employ chondroprogenitor cells in biomatrices appropriate for transplantation to cartilage surfaces appears feasible. A reduction in cytokine-mediated up-regulation of MMP gene expression as well as augmentation of cartilage ECM biosynthesis may also be possible by employing the principles of gene transfer using suitable vectors that establish long-term stable expression of genes which suppress MMPs while at the same time supporting cartilage ECM biosynthesis.