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Enhanced expression of tissue inhibitor of metalloproteinases-4 gene in human osteoarthritic synovial membranes and its differential regulation by cytokines in chondrocytes.
- Source :
-
The open rheumatology journal [Open Rheumatol J] 2011; Vol. 5, pp. 81-7. Date of Electronic Publication: 2011 Nov 29. - Publication Year :
- 2011
-
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.<br />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.<br />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.
Details
- Language :
- English
- ISSN :
- 1874-3129
- Volume :
- 5
- Database :
- MEDLINE
- Journal :
- The open rheumatology journal
- Publication Type :
- Academic Journal
- Accession number :
- 22216069
- Full Text :
- https://doi.org/10.2174/1874312901105010081