Skip to Main content Skip to Navigation
Journal articles

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

Abstract : 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(OCH 3)-Glu(OCH 3)-Val-Asp(OCH 3)-CH 2 F and caspase-9 inhibitor Z-Leu-Glu(OCH 3)-His-Asp(OCH 3)-CH 2 F 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 PGE 2 release. PD98059 and SB202190, but neither Z-DEVD FMK nor Z-LEHD FMK completely inhibited the SNP-mediated PGE 2 production. Analysis of interactions between PGE 2 and the cell death showed that PGE 2 enhanced the SNP-mediated cell death, whereas PGE 2 alone did not induce the chondrocyte death. These data indicate that NO-induced chondrocyte death signaling includes PGE 2 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 PGE 2 production. The results also demonstrate that exogenous PGE 2 may sensitize human OA chondrocytes to the cell death induced by NO.
Complete list of metadata

Cited literature [56 references]  Display  Hide  Download

https://hal.univ-lorraine.fr/hal-01705606
Contributor : Pascal Reboul <>
Submitted on : Friday, February 9, 2018 - 4:27:39 PM
Last modification on : Monday, July 20, 2020 - 12:33:14 PM

Links full text

Identifiers

Collections

Citation

Kohei Notoya, Dragan Jovanovic, P. Reboul, Johanne Martel-Pelletier, François Mineau, et al.. The Induction of Cell Death in Human Osteoarthritis Chondrocytes by Nitric Oxide Is Related to the Production of Prostaglandin E 2 Via the Induction of Cyclooxygenase-2. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2000, 165 (6), pp.3402-3410. ⟨10.4049/jimmunol.165.6.3402⟩. ⟨hal-01705606⟩

Share

Metrics

Record views

109