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 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 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.