Induction of apoptosis in bovine articular chondrocyte by prostaglandin E2 through cAMP-dependent pathway

Objective: Regulation of important biological processes such as proliferation and differentiation of articular chondrocytes is known to be mediated by prostaglandin E-2 (PGE(2)) in both normal and pathological states. Articular chondrocytes also undergo apoptosis, a biological phenomenon implicated in many physiological processes. Whether or not PGE(2) induces apoptosis in articular chondrocytes, however, is not known. Design: Bovine articular chondrocytes were cultured with or without PGE(2) for 24 h and amounts of fragmented DNA, which is a distinct characteristic of apoptosis, were measured by enzyme-linked immunosorbent assay. Also effect of cyclic AMP (cAMP), which is one of the intracellular downstream mediator of PGE(2), on chondrocyte apoptosis was investigated. Results: Administration of exogenous PGE(2) on bovine articular cartilage grown as a monolayer culture resulted in the induction of DNA fragmentation. This DNA fragmentation was accompanied with a marked dose-dependent increase in intracellular cAMP. Also cultured cells were treated with cAMP analogue, dibutyryl-cAMP or forskolin, a direct activator of adenylate cyclase, and the incidence of apoptosis in the chondrocytes was determined. As well as PGE(2), dibutyryl-cAMP and forskolin stimulated chondrocyte DNA fragmentation. Conclusions: It is the first report that PGE, can induce articular chondrocyte apoptosis in vitro. It is also suggest that apoptosis of chondrocytes by PGE, is linked with cAMP-dependent pathway. (C) 2000 OsteoArthritis Research Society International.