Pharmacologic Interventions for Preventing Chondrocyte Apoptosis in Rheumatoid Arthritis and Osteoarthritis

Chronic inflammation drives the progression of rheumatoid arthritis (RA) and osteo - arthritis (OA) to synovial joint failure. The inflammatory state in both musculoskeletal diseases is associated with significantly elevated levels of pro-inflammatory cytokines in joint synovial fluid, which is best exemplified by increases in interleukin-1β (IL-1β), IL-6, IL-17, tumor necrosis factor-α, among others, as well as increased activity of soluble mediators such as nitric oxide and certain growth factors including vascular endothe lial growth factor and fibroblast growth factor. The multitude of these factors activate chondrocyte signal transduction pathways resulting in programmed cell death, other wise known as apoptosis as well as compromising chondrocyte autophagy. Importantly, chondrocyte apoptosis causes a loss of articular cartilage vitality which dampens carti lage repair mechanisms because at present, the possibility that chondrocyte progenitor cells could replace those differentiated chondrocytes lost via apoptosis remains debat -able. Certain pharmacologic interventions which have been proven to induce apoptosis in various cancer cell studies in vitro suggest the possibility that drugs could be devel oped to specifically suppress or completely inhibit chondrocyte apoptosis in RA and OA cartilage. This review supports that contention and indicates that apoptosis can be inhibited by identifying novel cellular targets which promote apoptosis and autophagy.