HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 17, 15319-15325, April 25, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/17/15319    most recent M212520200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yoon, J.-B. Articles by Chun, J.-S. Search for Related Content PubMed PubMed Citation Articles by Yoon, J.-B. Articles by Chun, J.-S. Social Bookmarking                      What's this?

Non-steroidal Anti-inflammatory Drugs Inhibit Nitric Oxide-induced Apoptosis and Dedifferentiation of Articular Chondrocytes Independent of Cyclooxygenase Activity^*

Joo-Byoung Yoon, Song-Ja Kim, Sang-Gu Hwang, Sunghoe Chang, Shin-Sung Kang^§¶, and Jang-Soo Chun

From the  Department of Life Science, Kwangju Institute of Science and Technology; Buk-Gu, Gwangju 500-712, Korea, and ^§ Department of Biology, Kyungpook National University, Daegu 702-701, Korea

Nitric oxide (NO) causes apoptosis and dedifferentiation of articular chondrocytes by the modulation of extracellular signal-regulated kinase (ERK), p38 kinase, and protein kinase C (PKC)  and -. In this study, we investigated the effects and mechanisms of non-steroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, ketoprofen, ibuprofen, sulindac sulfide, and flurbiprofen, in NO-induced apoptosis and dedifferentiation of articular chondrocytes. We found that all of the examined NSAIDs inhibited apoptosis and dedifferentiation. NO production in chondrocytes caused activation of ERK-1/2 and p38 kinase, which oppositely regulate apoptosis and dedifferentiation. NO production also caused inhibition of PKC and - independent of and dependent on, respectively, p38 kinase, which is required for apoptosis and dedifferentiation. Among the signaling molecules modulated by NO, NSAIDs blocked NO-induced activation of p38 kinase, potentiated ERK activation, and blocked inhibition of PKC and -. NSAIDs also inhibited some of the apoptotic signaling that is downstream of p38 kinase and PKC, such as NFB activation, p53 accumulation, and caspase-3 activation. The inhibitory effects of NSAIDs on apoptosis and dedifferentiation were independent of the inhibition of cyclooxygenase (COX)-2 and prostaglandin E₂ (PGE₂) production, as evidenced by the observation that specific inhibition of COX-2 activity and PGE₂ production or exogenous PGE₂ did not affect NO-induced apoptosis and dedifferentiation. Taken together, our results indicate that NSAIDs block NO-induced apoptosis and dedifferentiation of articular chondrocytes by the modulation of ERK, p38 kinase, and PKC and - in a manner independent of their ability to inhibit COX-2 and PGE₂ production.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				M M Conradie, H de Wet, D D R Kotze, J M Burrin, F S Hough, and P A Hulley Vanadate prevents glucocorticoid-induced apoptosis of osteoblasts in vitro and osteocytes in vivo J. Endocrinol., November 1, 2007; 195(2): 229 - 240. [Abstract] [Full Text] [PDF]

				C Boileau, J Martel-Pelletier, J Brunet, D Schrier, C Flory, M Boily, and J-P Pelletier PD-0200347, an {alpha}2{delta} ligand of the voltage gated calcium channel, inhibits in vivo activation of the Erk1/2 pathway in osteoarthritic chondrocytes: a PKC{alpha} dependent effect Ann Rheum Dis, May 1, 2006; 65(5): 573 - 580. [Abstract] [Full Text] [PDF]

				C Boileau, J-P Pelletier, G Tardif, H Fahmi, S Laufer, M Lavigne, and J Martel-Pelletier The regulation of human MMP-13 by licofelone, an inhibitor of cyclo-oxygenases and 5-lipoxygenase, in human osteoarthritic chondrocytes is mediated by the inhibition of the p38 MAP kinase signalling pathway Ann Rheum Dis, June 1, 2005; 64(6): 891 - 898. [Abstract] [Full Text] [PDF]

				S. Ozgocmen, O. Ardicoglu, H. Erdogan, E. Fadillioglu, and H. Gudul In Vivo Effect of Celecoxib and Tenoxicam on Oxidant/Anti-oxidant Status of Patients with Knee Osteoarthritis Ann. Clin. Lab. Sci., April 1, 2005; 35(2): 137 - 143. [Abstract] [Full Text] [PDF]

				S.-G. Hwang, S.-S. Yu, J.-H. Ryu, H.-B. Jeon, Y.-J. Yoo, S.-H. Eom, and J.-S. Chun Regulation of {beta}-Catenin Signaling and Maintenance of Chondrocyte Differentiation by Ubiquitin-independent Proteasomal Degradation of {alpha}-Catenin J. Biol. Chem., April 1, 2005; 280(13): 12758 - 12765. [Abstract] [Full Text] [PDF]

				S.-G. Hwang, J.-H. Ryu, I.-C. Kim, E.-H. Jho, H.-C. Jung, K. Kim, S.-J. Kim, and J.-S. Chun Wnt-7a Causes Loss of Differentiated Phenotype and Inhibits Apoptosis of Articular Chondrocytes via Different Mechanisms J. Biol. Chem., June 18, 2004; 279(25): 26597 - 26604. [Abstract] [Full Text] [PDF]

				S.-J. Kim, S.-G. Hwang, I.-C. Kim, and J.-S. Chun Actin Cytoskeletal Architecture Regulates Nitric Oxide-induced Apoptosis, Dedifferentiation, and Cyclooxygenase-2 Expression in Articular Chondrocytes via Mitogen-activated Protein Kinase and Protein Kinase C Pathways J. Biol. Chem., October 24, 2003; 278(43): 42448 - 42456. [Abstract] [Full Text] [PDF]

				C.-D. Oh and J.-S. Chun Signaling Mechanisms Leading to the Regulation of Differentiation and Apoptosis of Articular Chondrocytes by Insulin-like Growth Factor-1 J. Biol. Chem., September 19, 2003; 278(38): 36563 - 36571. [Abstract] [Full Text] [PDF]