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PPAR Research
Volume 2010, Article ID 635912, 11 pages
http://dx.doi.org/10.1155/2010/635912
Research Article

Activation of PPARs , / , and Impairs TGF- 1-Induced Collagens' Production and Modulates the TIMP-1/MMPs Balance in Three-Dimensional Cultured Chondrocytes

1Laboratoire de Physiologie et Pharmacologie Articulaires (LPPA), UMR 7561 CNRS-UHP Nancy 1, avenue de la Forêt de Haye, BP 184, 54505 Vandœuvre-lès-Nancy Cedex, France
2Laboratoire de Biophotonique et Pharmacologie-UMR CNRS 7213, Faculté de Pharmacie, 74 route du Rhin, BP 60024, 67401 ILLKIRCH Cedex, France

Received 2 May 2010; Revised 13 July 2010; Accepted 30 July 2010

Academic Editor: Beata Lecka-Czernik

Copyright © 2010 Paul-Emile Poleni et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background and Purpose. We investigated the potency of Peroxisome Proliferators-Activated Receptors (PPARs) , / , and agonists to modulate Transforming Growth Factor- 1 (TGF- 1-) induced collagen production or changes in Tissue Inhibitor of Matrix Metalloproteinase- (TIMP-) 1/Matrix Metalloproteinase (MMP) balance in rat chondrocytes embedded in alginate beads. Experimental Approach. Collagen production was evaluated by quantitative Sirius red staining, while TIMP-1 protein levels and global MMP (-1, -2, -3, -7, and -9) or specific MMP-13 activities were measured by ELISA and fluorigenic assays in culture media, respectively. Levels of mRNA for type II collagen, TIMP-1, and MMP-3 & 13 were quantified by real-time PCR. Key Results. TGF- 1 increased collagen deposition and type II collagen mRNA levels, while inducing TIMP-1 mRNA and protein expression. In contrast, it decreased global MMP or specific MMP-13 activities, while decreasing MMP-3 or MMP-13 mRNA levels. PPAR agonists reduced most of the effects of TGF- 1 on changes in collagen metabolism and TIMP-1/MMP balance in rat in a PPAR-dependent manner, excepted for Wy14643 on MMP activities. Conclusions and Implications. PPAR agonists reduce TGF- 1-modulated ECM turnover and inhibit chondrocyte activities crucial for collagen biosynthesis, and display a different inhibitory profile depending on selectivity for PPAR isotypes.