Mechanisms of chondrocyte apoptosis

This study addresses the occurrence and significance of chondrocyte apoptos is in the pathogenesis of cartilage destruction. Chondrocyte apoptosis can be induced in vitro by nitric oxide donors, but not by pro-inflammatory cyt okines, such as IL-l or TNF. A subset of chondrocytes, located in the super ficial zone of cartilage, expresses the Fas antigen. Activation of the Fas receptor triggers apoptosis in these cells. In human and experimental osteo arthritis (OA) induced in rabbits by anterior cruciate ligament transection increased numbers of chondrocytes were undergoing apoptosis. Cartilage are as that contained apoptotic cells showed proteoglycan depletion and the num ber of apoptotic cells was significantly correlated with the levels of nitr ic oxide production and with the severity of OA. Articular cartilage is not vascularized and does not contain mononuclear phagocytes. There is, thus, no apparent mechanism for the clearance of apoptotic bodies. Chondrocyte-de rived apoptotic bodies produced pyrophosphate and precipitated calcium. The se results suggest that chondrocyte-derived apoptotic bodies express functi onal properties that may contribute to the pathologic cartilage degradation and calcification. Inhibition of chondrocyte apoptosis may be of therapeut ic value after cartilage injury and in arthritis.