The Influence of Mechanical Stress and Inflammation on the Metabolism and Degeneration of the Meniscus and Potential Drug Therapy

Injuries of the knee joint and in particular of the menisci are very common in orthopedic and trauma surgery. The menisci are subjected to significant mechanical stresses along with the articular cartilage and serve to distribute loads across the tibial plateau. These mechanical forces can alter the metabolic activity of articular cartilage and menisci. For example, exercise increases collagen and proteoglycan contents in menisci, while joint immobilization inhibits collagen accumulation in healing menisci. However, little is known of the sequence of biomechanical and biochemical events linking mechanical stress to inflammatory or degenerative changes of the meniscus. The goal of this study is to determine the influence of dynamic mechanical compression on matrix synthesis in meniscal explants cultured in the presence of the pro-inflammatory cytokine interleukin-1. We also investigate the matrix biosynthesis and turnover of meniscal fibrochondrocytes mediated through the endogenous production of nitric oxide or prostaglandin E2 . Time course and effects of stress magnitude of physiological levels of intermittent compression on production of various parameters in meniscal explants will be measured. Immunoblots will be carried out using monoclonal antibodies and release of newly synthesized labeled matrix components will be determined in the media. By investigation of newly discovered pathways in the metabolism of menisci we are able to determine the influence of particular mediators and influence the degeneration and wear of the menisci. This will contribute to a better knowledge of meniscal physiology and meniscal healing. In addition a possibility to prevent meniscal degeneration by administration of drugs could be offered.