{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:30:20Z","timestamp":1786977020333,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2012,9,28]],"date-time":"2012-09-28T00:00:00Z","timestamp":1348790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2012,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To determine the expression of suppressor of cytokine signaling 3 (SOCS\u20103) in human articular chondrocytes and its functional consequences.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Chondrocytes were isolated from the cartilage of patients with osteoarthritis (OA), patients with rheumatoid arthritis (RA), and trauma patients and from the healthy cartilage of patients with a femoral neck fracture. The human chondrocyte cell line G6 and primary bovine chondrocytes were used in validation experiments. SOCS\u20103 messenger RNA (mRNA) expression was measured by quantitative polymerase chain reaction, and SOCS\u20103 protein levels were determined by Western blotting and immunohistochemical analysis. To ascertain the role of SOCS\u20103 in the chondrocyte response to interleukin\u20101\u03b2 (IL\u20101\u03b2) or lipopolysaccharide (LPS), the expression of\n                      <jats:italic>SOCS3<\/jats:italic>\n                      was either reduced by small interfering RNA or enhanced by viral transduction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The expression of SOCS\u20103 mRNA (but not that of SOCS\u20101 mRNA) was significantly enhanced in chondrocytes obtained from OA cartilage (mean \u00b1 SD \u0394C\n                      <jats:sub>t<\/jats:sub>\n                      3.4 \u00b1 1.0) and RA cartilage (\u0394C\n                      <jats:sub>t<\/jats:sub>\n                      3.4 \u00b1 1.4) compared with cartilage obtained from patients with femoral neck fracture (\u0394C\n                      <jats:sub>t<\/jats:sub>\n                      5.3 \u00b1 1.2). The expression of\n                      <jats:italic>SOCS3<\/jats:italic>\n                      correlated significantly with that of other genes known to be expressed in arthritic chondrocytes, such as\n                      <jats:italic>MMP13<\/jats:italic>\n                      (r = 0.743),\n                      <jats:italic>ADAMTS4<\/jats:italic>\n                      (r = 0.779), and\n                      <jats:italic>ADAMTS5<\/jats:italic>\n                      (r = 0.647), and an inverse relationship was observed with\n                      <jats:italic>COL2A1<\/jats:italic>\n                      (r = \u22120.561). Up\u2010regulation of SOCS\u20103 by IL\u20101 in G6 chondrocytes and its spontaneous expression in OA chondrocytes were reduced by mithramycin, a specific inhibitor of transcription factor Sp\u20101. Overexpression of SOCS\u20103 in bovine chondrocytes reduced IL\u20101\u2013 and LPS\u2010induced nitric oxide production and insulin\u2010like growth factor 1\u2013induced proteoglycan synthesis. Interestingly, a similar impairment of function was observed in OA chondrocytes, which was partially restored by SOCS\u20103 gene knockdown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study demonstrated that both SOCS\u20103 mRNA and SOCS\u20103 protein are expressed in human arthritic chondrocytes and affect cellular responses involved in cartilage pathology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.34529","type":"journal-article","created":{"date-parts":[[2012,5,10]],"date-time":"2012-05-10T14:47:39Z","timestamp":1336661259000},"page":"3313-3323","source":"Crossref","is-referenced-by-count":26,"title":["Enhanced suppressor of cytokine signaling 3 in arthritic cartilage dysregulates human chondrocyte function"],"prefix":"10.1002","volume":"64","author":[{"given":"Fons A. 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