M. Miwa et al., Induction of apoptosis in bovine articular chondrocyte by prostaglandin E-2 through cAMP-dependent pathway, OSTEO CART, 8(1), 2000, pp. 17-24
Objective: Regulation of important biological processes such as proliferati
on and differentiation of articular chondrocytes is known to be mediated by
prostaglandin E-2 (PGE(2)) in both normal and pathological states. Articul
ar 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 effe
ct of cyclic AMP (cAMP), which is one of the intracellular downstream media
tor of PGE(2), on chondrocyte apoptosis was investigated.
Results: Administration of exogenous PGE(2) on bovine articular cartilage g
rown as a monolayer culture resulted in the induction of DNA fragmentation.
This DNA fragmentation was accompanied with a marked dose-dependent increa
se in intracellular cAMP. Also cultured cells were treated with cAMP analog
ue, dibutyryl-cAMP or forskolin, a direct activator of adenylate cyclase, a
nd the incidence of apoptosis in the chondrocytes was determined. As well a
s PGE(2), dibutyryl-cAMP and forskolin stimulated chondrocyte DNA fragmenta
tion.
Conclusions: It is the first report that PGE, can induce articular chondroc
yte apoptosis in vitro. It is also suggest that apoptosis of chondrocytes b
y PGE, is linked with cAMP-dependent pathway. (C) 2000 OsteoArthritis Resea
rch Society International.