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Huang W, Mabrouk ME, Sylvester J, et al. Enhanced expression of tissue inhibitor of metalloproteinases-4 gene in human osteoarthritic synovial membranes and its differential regulation by cytokines in chondrocytes. Open Rheumatol J. 2011;5:81-7doi: 10.2174/1874312901105010081.
Huang, W., Mabrouk, M. E., Sylvester, J., Dehnade, F., & Zafarullah, M. (2011). Enhanced expression of tissue inhibitor of metalloproteinases-4 gene in human osteoarthritic synovial membranes and its differential regulation by cytokines in chondrocytes. The open rheumatology journal, 581-7. https://doi.org/10.2174/1874312901105010081
Huang, Wensheng, et al. "Enhanced expression of tissue inhibitor of metalloproteinases-4 gene in human osteoarthritic synovial membranes and its differential regulation by cytokines in chondrocytes." The open rheumatology journal vol. 5 (2011): 81-7. doi: https://doi.org/10.2174/1874312901105010081
Huang W, Mabrouk ME, Sylvester J, Dehnade F, Zafarullah M. Enhanced expression of tissue inhibitor of metalloproteinases-4 gene in human osteoarthritic synovial membranes and its differential regulation by cytokines in chondrocytes. Open Rheumatol J. 2011;5:81-7. doi: 10.2174/1874312901105010081. Epub 2011 Nov 29. PMID: 22216069; PMCID: PMC3245407.
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Open Rheumatol J. 2011;5:81-7. doi: 10.2174/1874312901105010081. Epub 2011 Nov 29.

Enhanced expression of tissue inhibitor of metalloproteinases-4 gene in human osteoarthritic synovial membranes and its differential regulation by cytokines in chondrocytes.

The open rheumatology journal

Wensheng Huang, Mohammed El Mabrouk, Judith Sylvester, Faramaze Dehnade, Muhammad Zafarullah

Affiliations

  1. Department of Medicine, University of Montreal and Research Center of CHUM (CRCHUM) Notre-Dame Hospital, Montreal, Quebec, H2L 4M1, Canada.

PMID: 22216069 PMCID: PMC3245407 DOI: 10.2174/1874312901105010081

Abstract

OBJECTIVE: Tissue inhibitors of metalloproteinases (TIMPs) are multi-functional proteins with matrix metalloproteinases-inhibiting activities. We studied expression of anti-inflammatory, TIMP-4 gene in human joint tissues and its regulation by arthritis-associated cytokines.

RESULTS: TIMP-4 RNA expression originating from synovial fibroblasts was significantly (2.4 fold; p<0.001) elevated in 8 osteoarthritic (OA) versus 7 non-arthritic synovial membranes. Non-arthritic and OA femoral head and knee chondrocytes displayed substantial but variably constitutive expression of the TIMP-4 mRNA. In articular chondrocytes, transforming growth factor beta (TGF-β1) and oncostatin M (OSM) upregulated TIMP-4 RNA and protein expression while interleukin-1 (IL-1β) and tumor necrosis factor alpha (TNF-α) did not, suggesting differential regulation by arthritis-associated cytokines. Interleukin 17 (IL-17) mildly induced TIMP-4 mRNA. TGF-β1 induction of TIMP-4 expression was partly inhibited by ERK pathway and Sp1 transcription factor inhibitors.

CONCLUSION: Enhanced TIMP-4 gene expression in OA synovial membranes and cartilage may be due to induction by TGF-β1, OSM and IL-17, suggesting its pathophysiological role in tissue remodeling in human joints. TGF-β1 induction of TIMP-4 expression is mediated partly by ERK pathway and Sp1 transcription factor.

Keywords: Osteoarthritis; TIMP-4; chondrocytes; cytokines.; synovium

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