Activation of PPARs α, β/δ, and γ Impairs TGF-β1-Induced Collagens' Production and Modulates the TIMP-1/MMPs Balance in Three-Dimensional Cultured Chondrocytes.
Activation of PPARs α, β/δ, and γ Impairs TGF-β1-Induced Collagens' Production and Modulates the TIMP-1/MMPs Balance in Three-Dimensional Cultured Chondrocytes.
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DOI:
10.1155/2010/635912
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发表时间:
2010
期刊:
影响因子:
2.9
通讯作者:
Bianchi A
中科院分区:
文献类型:
--
作者:
Poleni PE;Etienne S;Velot E;Netter P;Bianchi A
Background and Purpose. We investigated the potency of Peroxisome Proliferators-Activated Receptors (PPARs) α, β/δ, and γ agonists to modulate Transforming Growth Factor-β1 (TGF-β1-) 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-β1 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-β1 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-β1-modulated ECM turnover and inhibit chondrocyte activities crucial for collagen biosynthesis, and display a different inhibitory profile depending on selectivity for PPAR isotypes.
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影响因子:
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作者:
Ghosh, AK;Bhattacharyya, S;Varga, J
通讯作者:
Varga, J
影响因子:
7.7
作者:
Park, CW;Kim, HW;Breyer, MD
通讯作者:
Breyer, MD
DOI:
10.1302/0301-620x.87b1.14154
发表时间:
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影响因子:
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作者:
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通讯作者:
Bentley, G
影响因子:
29.4
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通讯作者:
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影响因子:
2.8
作者:
Qi, WN;Scully, SP
通讯作者:
Scully, SP