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

Miwa, Masaichi; Saura, Ryuichi; Hirata, Soichiro; Hayashi, Yujiro; Mizuno, Kosaku; Itoh, Hisashi

doi:10.1053/joca.1999.0266

Cited by 99 publications

(73 citation statements)

References 42 publications

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“…Increased apoptosis has been observed in chondrocytes treated with exogenous PGE 2 and is coupled with increased cAMP (46,47); however, effects on mitochondria have not been reported. Conversely, PGE 2 has been shown to mediate apoptotic resistance in other cell types, including cancer cells (48,49) and gastric mucosal cells (50) via mitochondrion-dependent pathways.…”

Section: Discussionmentioning

confidence: 97%

The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production

Dave

Attur

Palmer

et al. 2008

Arthritis & Rheumatism

119

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Objective. To determine the effects of the antioxidant resveratrol on the functions of human chondrocytes in osteoarthritis (OA).Methods. Chondrocytes and cartilage explants were isolated from OA patients undergoing knee replacement surgery. Effects of resveratrol in the presence or absence of interleukin-1␤ (IL-1␤) stimulation were assessed by measurement of prostaglandin E 2 (PGE 2 ) and leukotriene B 4 (LTB 4 ) synthesis, cyclooxygenase (COX) activity, matrix metalloproteinase (MMP) expression, and proteoglycan production. To explore the mechanisms of action of resveratrol, its effects on mitochondrial function and apoptosis were examined by assessing mitochondrial membrane potential, ATP levels, cytochrome c release, and annexin V staining.Results. Resveratrol inhibited both spontaneous and IL-1␤-induced PGE 2 production by >20% (P < 0.05) and by 80% (P < 0.001), respectively; similarly, LTB 4 production was reduced by >50% (P < 0.05). The production of PGE 2 was inhibited via a 70-90% suppression of COX-2 expression and enzyme activity (P < 0.05). Resveratrol also promoted anabolic effects in OA explant cultures, by elevating proteoglycan synthesis and decreasing production of MMPs 1, 3, and 13. Pretreatment of OA chondrocytes with resveratrol blocked mitochondrial membrane depolarization, loss of mitochondrial biomass, and IL-1␤-induced ATP depletion. Similarly, IL-1␤-mediated induction of the apoptotic markers cytochrome c and annexin V was also inhibited by resveratrol. Exogenous addition of PGE 2 abolished the protective effects of resveratrol on mitochondrial membrane integrity, ATP levels, expression of apoptotic markers, and DNA fragmentation.Conclusion. Resveratrol protects against IL-1␤-induced catabolic effects and prevents chondrocyte apoptosis via its inhibition of mitochondrial membrane depolarization and ATP depletion. These beneficial effects of resveratrol are due, in part, to its capacity to inhibit COX-2-derived PGE 2 synthesis. Resveratrol may therefore protect against oxidant injury and apoptosis, which are main features of progressive OA.

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Section: Discussionmentioning

confidence: 97%

The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production

Dave

Attur

Palmer

et al. 2008

Arthritis & Rheumatism

119

View full text Add to dashboard Cite

show abstract

“…In contrast, low concentrations of PGE 2 may downregulate collagenases and collagen 2A1 cleavage [38]. PGE 2 may enhance chondrocyte death [39] and induce apoptosis in bovine articular chondrocytes through the cAMP pathway [40]. In this study, we investigated the effects of HO-1 induction on IL-1-stimulated PGE 2 production in primary OA chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

Heme oxygenase-1 induction modulates microsomal prostaglandin E synthase-1 expression and prostaglandin E2 production in osteoarthritic chondrocytes

Megías

Guillén²,

Clérigues³

et al. 2009

Biochemical Pharmacology

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“…A recent study using bovine normal articular chondrocyte has demonstrated that even PGE 2 itself induced DNA fragmentation of the cells, as determined by ELISA (55). This controversy may be due to differences in culture conditions and/or cartilage specimen used for cell culture.…”

Section: Discussionmentioning

confidence: 99%

The Induction of Cell Death in Human Osteoarthritis Chondrocytes by Nitric Oxide Is Related to the Production of Prostaglandin E2 Via the Induction of Cyclooxygenase-2

Notoya

Jovanović

Reboul

et al. 2000

The Journal of Immunology

168

136

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There is increasing evidence suggesting that chondrocyte death may contribute to the progression of osteoarthritis (OA). This study focused on the characterization of signaling cascade during NO-induced cell death in human OA chondrocytes. The NO generator, sodium nitroprusside (SNP), promoted chondrocyte death in association with DNA fragmentation, caspase-3 activation, and down-regulation of Bcl-2. Both caspase-3 inhibitor Z-Asp(OCH3)-Glu(OCH3)-Val-Asp(OCH3)-CH2F and caspase-9 inhibitor Z-Leu-Glu(OCH3)-His-Asp(OCH3)-CH2F prevented the chondrocyte death. Blocking the mitogen-activated protein kinase pathway by the mitogen-activated protein kinase kinase 1/2 inhibitor PD98059 or p38 kinase inhibitor SB202190 also inhibited the SNP-mediated cell death, suggesting possible requirements of both extracellular signal-related protein kinase 1/2 and p38 kinase for the NO-induced cell death. Furthermore, the selective inhibition of cyclooxygenase (COX)-2 by NS-398 or the inhibition of COX-1/COX-2 by indomethacin blocked the SNP-induced cell death. The chondrocyte death induced by SNP was associated with an overexpression of COX-2 protein (as determined by Western blotting) and an increase in PGE2 release. PD98059 and SB202190, but neither Z-DEVD FMK nor Z-LEHD FMK completely inhibited the SNP-mediated PGE2 production. Analysis of interactions between PGE2 and the cell death showed that PGE2 enhanced the SNP-mediated cell death, whereas PGE2 alone did not induce the chondrocyte death. These data indicate that NO-induced chondrocyte death signaling includes PGE2 production via COX-2 induction and suggest that both extracellular signal-related protein kinase 1/2 and p38 kinase pathways are upstream signaling of the PGE2 production. The results also demonstrate that exogenous PGE2 may sensitize human OA chondrocytes to the cell death induced by NO.

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

Abstract: It is the first report that PGE(2) can induce articular chondrocyte apoptosis in vitro. It is also suggest that apoptosis of chondrocytes by PGE(2) is linked with cAMP-dependent pathway.

Cited by 99 publications

References 42 publications

The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production

The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production

Heme oxygenase-1 induction modulates microsomal prostaglandin E synthase-1 expression and prostaglandin E2 production in osteoarthritic chondrocytes

The Induction of Cell Death in Human Osteoarthritis Chondrocytes by Nitric Oxide Is Related to the Production of Prostaglandin E2 Via the Induction of Cyclooxygenase-2

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