Retinoic acid blocks pro-inflammatory cytokine-induced matrix metalloproteinase production by down-regulating JNK-AP-1 signaling in human chondrocytes

Ling Jun Ho, Leou Chyr Lin, Li Feng Hung, Shyu Jye Wang, Chian Her Lee, Deh Ming Chang, Jenn Haung Lai, Tong Yuan Tai

研究成果: 雜誌貢獻文章

54 引文 斯高帕斯(Scopus)

摘要

The development of osteoarthritis (OA) has recently been implicated as a result of immune-mediated damage of chondrocytes and their supporting matrixes. Pro-inflammatory cytokines like interleukin (IL)-1 and tumor necrosis factor alpha (TNF-α) play pivotal roles in immunopathogenesis of OA. Because vitamins preserving anti-oxidative effects are suggested to provide protection in OA patients from joint damage, in the present study, we examined the effects and mechanisms of all-trans retinoic acid (t-RA) in suppressing pro-inflammatory cytokine-induced matrix metalloproteinases (MMPs) production in human chondrocytes. Chondrocytes were prepared from cartilage specimens of OA patients receiving total hip or total knee replacement. The protein concentration was measured by ELISA, the mRNA expression by reverse transcriptase-polymerase chain reaction, the protein expression by Western blotting, the transcription factor DNA-binding activity by electrophoretic mobility shift assay and the protein kinase activity by kinase assay. We showed that both MMP-1 and MMP-13 mRNA expression, protein production and enzyme activity induced by either IL-1 or TNF-α were suppressed by t-RA or different retinoid derivatives. The molecular investigation revealed that the t-RA-mediated suppression was likely through blocking p38 kinase and c-Jun N-terminal kinase-activator protein-1 signaling pathways. In contrast, t-RA had no effect on extracellular signal-regulated kinase activity, nuclear factor kappaB (NF-κB) DNA-binding activity and IκBα degradation. Furthermore, we showed that t-RA could reduce IL-1-induced TNF-α production in chondrocytes. Our results suggest that vitamin A may protect OA patients from pro-inflammatory cytokine-mediated damage of chondrocytes and their supporting matrixes.

原文英語
頁(從 - 到)200-208
頁數9
期刊Biochemical Pharmacology
70
發行號2
DOIs
出版狀態已發佈 - 七月 15 2005
對外發佈Yes

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ASJC Scopus subject areas

  • Pharmacology

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