ArticleThe open rheumatology journal2011
Enhanced expression of tissue inhibitor of metalloproteinases-4 gene in human osteoarthritic synovial membranes and its differential regulation by cytokines in chondrocytes.
Article in The open rheumatology journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 2 of them syntheses that pooled it.
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Who cites it
8 citing papers in PubMed, 2 syntheses or guidelines pooled it, 14 citations in OpenAlex.
- Protein Biomarkers in Venous Leg Ulcer Fluid: A Systematic Review.International wound journal · 2025Pooled it
- Identifying Novel Osteoarthritis-Associated Genes in Human Cartilage Using a Systematic Meta-Analysis and a Multi-Source Integrated Network.International journal of molecular sciences · 2022Pooled it
- The TIMP protein family: diverse roles in pathophysiology.American journal of physiology. Cell physiology · 2024Review
- Impact of chitosan membrane culture on the expression of pro- and anti-inflammatory cytokines in mesenchymal stem cells.Experimental and therapeutic medicine · 2020Article
- Elastin homeostasis is altered with pelvic organ prolapse in cultures of vaginal cells from a lysyl oxidase-like 1 knockout mouse model.Physiological reports · 2020Article
- Crosstalk between Smad2/3 and specific isoforms of ERK in TGF-β1-induced TIMP-3 expression in rat chondrocytes.Journal of cellular and molecular medicine · 2017Article
- DA-Raf-dependent inhibition of the Ras-ERK signaling pathway in type 2 alveolar epithelial cells controls alveolar formation.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Complex temporal changes in TGFβ oncogenic signaling drive thyroid carcinogenesis in a mouse model.Carcinogenesis · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTissue 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.
resultsTIMP-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.
conclusionEnhanced 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.
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