15-deoxy-delta^12,14-prostaglandin J₂ induces apoptosis in human articular chondrocytes

A derivative of prostaglandin D₂, 15-deoxy-delta^12,14-prostaglandin J₂ (15d-PGJ₂) is one of the cyclooxygenase (COX) products in the arachidonic acid cascade. PGJ₂ series have been reported to exert various bioactivities, including modulation of viability of a wide array of cells, and are known to act as an active ligand for the nuclear receptor peroxisome proliferator-activated proteins gamma. 15d-PGJ₂ is also suggested to play a role in cartilage metabolism; however, this issue is still not fully understood. We investigated the potential role of the 15d-PGJ₂ in the induction of apoptotic death in human articular chondrocytes. Cartilage samples were obtained from patients who underwent joint surgery. Articular chondrocytes were isolated from the cartilage by mincing and enzymatic treatment, and the cells were further cultured in a monolayer system in vitro. Confluent cells at the first passage were stimulated with the 15d-PGJ₂, and the effect of the 15d-PGJ₂ in the viability of chondrocytes were assessed using Hoechst staining, flow cytometric analysis and the caspase-3 activity assay. The results showed that the 15d-PGJ₂was potent to induce chondrocyte apoptosis characterized by cellular shrinkage and nuclear condensation, along with an increased activity of caspase-3 in the treated cells. Involvement of the 15d-PGJ₂ in chondrocyte apoptosis may have an important implication in the pathogenesis of inflammatory and degenerative joint diseases.