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

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)200-208
Number of pages9
JournalBiochemical Pharmacology
Volume70
Issue number2
DOIs
Publication statusPublished - Jul 15 2005
Externally publishedYes

Fingerprint

Transcription Factor AP-1
Chondrocytes
Tretinoin
Matrix Metalloproteinases
Osteoarthritis
Cytokines
Interleukin-1
Tumor Necrosis Factor-alpha
Assays
Phosphotransferases
Matrix Metalloproteinase 13
Knee prostheses
Electrophoretic mobility
Knee Replacement Arthroplasties
Messenger RNA
Matrix Metalloproteinase 1
Proteins
JNK Mitogen-Activated Protein Kinases
Polymerase chain reaction
RNA-Directed DNA Polymerase

Keywords

  • Activator protein-1
  • C-Jun N-terminal kinase
  • Chondrocytes
  • Cytokines
  • Matrix metalloproteinases
  • Osteoarthritis

ASJC Scopus subject areas

  • Pharmacology

Cite this

Retinoic acid blocks pro-inflammatory cytokine-induced matrix metalloproteinase production by down-regulating JNK-AP-1 signaling in human chondrocytes. / Ho, Ling Jun; Lin, Leou Chyr; Hung, Li Feng; Wang, Shyu Jye; Lee, Chian Her; Chang, Deh Ming; Lai, Jenn Haung; Tai, Tong Yuan.

In: Biochemical Pharmacology, Vol. 70, No. 2, 15.07.2005, p. 200-208.

Research output: Contribution to journalArticle

Ho, Ling Jun ; Lin, Leou Chyr ; Hung, Li Feng ; Wang, Shyu Jye ; Lee, Chian Her ; Chang, Deh Ming ; Lai, Jenn Haung ; Tai, Tong Yuan. / Retinoic acid blocks pro-inflammatory cytokine-induced matrix metalloproteinase production by down-regulating JNK-AP-1 signaling in human chondrocytes. In: Biochemical Pharmacology. 2005 ; Vol. 70, No. 2. pp. 200-208.
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AU - Lin, Leou Chyr

AU - Hung, Li Feng

AU - Wang, Shyu Jye

AU - Lee, Chian Her

AU - Chang, Deh Ming

AU - Lai, Jenn Haung

AU - Tai, Tong Yuan

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KW - Cytokines

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