{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T23:18:06Z","timestamp":1780960686340,"version":"3.54.1"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,2,27]],"date-time":"2017-02-27T00:00:00Z","timestamp":1488153600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01\u2010AR054817"],"award-info":[{"award-number":["R01\u2010AR054817"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01\u2010AR063128"],"award-info":[{"award-number":["R01\u2010AR063128"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Degeneration of articular cartilage is central to the pathology of osteoarthritis (OA). However, the molecular mechanisms leading to these irreversible changes are still poorly understood. This study was undertaken to investigate how changes in the chondrocyte translational apparatus may contribute to the development and progression of knee OA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Articular cartilage from the knees of normal healthy subjects and patients with OA was used to analyze the activity of different components of the translational machinery. Chondrocytes isolated from lesional and nonlesional areas of the human OA cartilage were used to estimate the relative rate of protein synthesis by metabolic labeling. Experimental OA was induced by transection of the anterior cruciate ligament of rats to investigate changes in the translational apparatus associated with OA. The role of interleukin\u20101\u03b2 (IL\u20101\u03b2) signaling was assessed in vitro using rat articular chondrocytes. In human or rodent knee cartilage, messenger RNA expression was analyzed by quantitative polymerase chain reaction, and protein levels were determined by immunohistochemistry and Western blotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Several novel traits of OA chondrocytes were identified, including up\u2010regulation of the serine\/threonine kinases Akt\u20102 and Akt\u20103 at the posttranscriptional level and an increased rate of total protein synthesis, likely attributable to inactivation of eukaryotic initiation factor 4E binding protein 1 (4E\u2010BP1), a known repressor of cap\u2010dependent translation. Inactivation of 4E\u2010BP1 was dependent on the activity of mechanistic target of rapamycin and was crucial for the up\u2010regulation of protein synthesis in general and expression of matrix metalloproteinase 13 and ADAMTS\u20105 in particular. In addition, treatment of articular chondrocytes with IL\u20101\u03b2 led to inactivation of 4E\u2010BP1 and up\u2010regulation of protein synthesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Precise control of protein synthesis is vital for cartilage homeostasis, and its dysregulation contributes to the molecular pathology of OA. The results of this study therefore identify a novel set of potential therapeutic targets to ameliorate the effects of knee OA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.39947","type":"journal-article","created":{"date-parts":[[2016,10,7]],"date-time":"2016-10-07T08:58:50Z","timestamp":1475830730000},"page":"586-597","source":"Crossref","is-referenced-by-count":27,"title":["Increased Activity of the Chondrocyte Translational Apparatus Accompanies Osteoarthritic Changes in Human and Rodent Knee Cartilage"],"prefix":"10.1002","volume":"69","author":[{"given":"Olga","family":"Katsara","sequence":"first","affiliation":[{"name":"New York University Langone Medical Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mukundan","family":"Attur","sequence":"additional","affiliation":[{"name":"New York University Langone Medical Center New York New 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