Induction of apoptosis in bovine articular chondrocyte by prostaglandin E2through cAMP-dependent pathway

Abstract

Objective Regulation of important biological processes such as proliferation and differentiation of articular chondrocytes is known to be mediated by prostaglandin E2(PGE2) in both normal and pathological states. Articular chondrocytes also undergo apoptosis, a biological phenomenon implicated in many physiological processes. Whether or not PGE2induces apoptosis in articular chondrocytes, however, is not known.Design Bovine articular chondrocytes were cultured with or without PGE2for 24h 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 PGE2, on chondrocyte apoptosis was investigated.Results Administration of exogenous PGE2on 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 PGE2, dibutyryl-cAMP and forskolin stimulated chondrocyte DNA fragmentation.Conclusions It is the first report that PGE2can induce articular chondrocyte apoptosis in vitro. It is also suggest that apoptosis of chondrocytes by PGE2is linked with cAMP-dependent pathway.