{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1362544420344687488.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.2174/1874312901105010081"}},{"identifier":{"@type":"URI","@value":"https://openrheumatologyjournal.com/contents/volumes/V5/TORJ-5-81/TORJ-5-81.pdf"}},{"identifier":{"@type":"URI","@value":"https://openrheumatologyjournal.com/contents/volumes/V5/TORJ-5-81/TORJ-5-81.xml"}}],"dc:title":[{"@value":"Enhanced Expression of Tissue Inhibitor of Metalloproteinases-4 Gene in Human Osteoarthritic Synovial Membranes and Its Differential Regulation by Cytokines in Chondrocytes"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:sec>\n                    <jats:title>Objective:</jats:title>\n                    <jats:p>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.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:</jats:title>\n                    <jats:p>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.</jats:p>\n                  </jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:</jats:title>\n                    <jats:p>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.</jats:p>\n                  </jats:sec>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1382544420344687488","@type":"Researcher","foaf:name":[{"@value":"Wensheng Huang"}]},{"@id":"https://cir.nii.ac.jp/crid/1380025033204016259","@type":"Researcher","foaf:name":[{"@value":"Mohammed El Mabrouk"}]},{"@id":"https://cir.nii.ac.jp/crid/1380025033204016257","@type":"Researcher","foaf:name":[{"@value":"Judith Sylvester"}]},{"@id":"https://cir.nii.ac.jp/crid/1380025033204016256","@type":"Researcher","foaf:name":[{"@value":"Faramaze Dehnade"}]},{"@id":"https://cir.nii.ac.jp/crid/1380025033204016258","@type":"Researcher","foaf:name":[{"@value":"Muhammad Zafarullah"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"18743129"}],"prism:publicationName":[{"@value":"The Open Rheumatology Journal"}],"dc:publisher":[{"@value":"Bentham Science Publishers Ltd."}],"prism:publicationDate":"2011-11-29","prism:volume":"5","prism:number":"1","prism:startingPage":"81","prism:endingPage":"87"},"reviewed":"false","dc:rights":["https://creativecommons.org/licenses/by/4.0/legalcode"],"url":[{"@id":"https://openrheumatologyjournal.com/contents/volumes/V5/TORJ-5-81/TORJ-5-81.pdf"},{"@id":"https://openrheumatologyjournal.com/contents/volumes/V5/TORJ-5-81/TORJ-5-81.xml"}],"createdAt":"2011-12-09","modifiedAt":"2025-10-27","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360848658890699008","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"DA-Raf–dependent inhibition of the Ras-ERK signaling pathway in type 2 alveolar epithelial cells controls alveolar formation"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.2174/1874312901105010081"},{"@type":"CROSSREF","@value":"10.1073/pnas.1321574111_references_DOI_ApUzS0XGjJY4CEY2inWATMFFWCy"}]}