{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:46:41Z","timestamp":1787028401661,"version":"build-2736575974"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T00:00:00Z","timestamp":1499731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Austrians Science Fund","award":["P 25336-B13"],"award-info":[{"award-number":["P 25336-B13"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoarthritis (OA) is hallmarked by a progressive degradation of articular cartilage. Besides risk factors including trauma, obesity or genetic predisposition, inflammation has a major impact on the development of this chronic disease. During the course of inflammation, cytokines such as tumor necrosis factor-alpha(TNF-\u03b1) and interleukin (IL)-1\u03b2 are secreted by activated chondrocytes as well as synovial cells and stimulate the production of other inflammatory cytokines and matrix degrading enzymes. The mTORC1 inhibitor rapamycin is a clinical approved immunosuppressant and several studies also verified its chondroprotective effects in OA. However, the effect of blocking the mechanistic target of rapamycin complex (mTORC)1 on the inflammatory status within OA is not well studied. Therefore, we aimed to investigate if inhibition of mTORC1 by rapamycin can preserve and sustain chondrocytes in an inflammatory environment. Patient-derived chondrocytes were cultured in media supplemented with or without the mTORC1 inhibitor rapamycin. To establish an inflammatory environment, either TNF-\u03b1 or IL-1\u03b2 was added to the media (=OA-model). The chondroprotective and anti-inflammatory effects of rapamycin were evaluated using sulfated glycosaminoglycan (sGAG) release assay, Caspase 3\/7 activity assay, lactate dehydrogenase (LDH) assay and quantitative real time polymerase chain reaction (PCR). Blocking mTORC1 by rapamycin reduced the release and therefore degradation of sGAGs, which are components of the extracellular matrix secreted by chondrocytes. Furthermore, blocking mTORC1 in OA chondrocytes resulted in an enhanced expression of the main chondrogenic markers. Rapamycin was able to protect chondrocytes from cell death in an OA-model shown by reduced Caspase 3\/7 activity and diminished LDH release. Furthermore, inhibition of mTORC1 preserved the chondrogenic phenotype of OA chondrocytes, but also reduced inflammatory processes within the OA-model. This study highlights that blocking mTORC1 is a new and promising approach for treating OA. Low side effects make rapamycin an attractive implementation to existing therapeutic strategies. We showed that rapamycin\u2019s chondroprotective property might be due to an interference with IL-1\u03b2 triggered inflammatory processes.<\/jats:p>","DOI":"10.3390\/ijms18071494","type":"journal-article","created":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T11:13:11Z","timestamp":1499771591000},"page":"1494","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Rapamycin Maintains the Chondrocytic Phenotype and Interferes with Inflammatory Cytokine Induced Processes"],"prefix":"10.3390","volume":"18","author":[{"given":"Andrea De","family":"Luna-Preitschopf","sequence":"first","affiliation":[{"name":"Center for Regenerative Medicine and Orthopedics, Danube University Krems, 3500 Krems, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannes","family":"Zwickl","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine 2, University Hospital Krems, Karl Landsteiner University of Health Sciences, 3500 Krems, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Nehrer","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine and Orthopedics, Danube University Krems, 3500 Krems, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Hengstschl\u00e4ger","sequence":"additional","affiliation":[{"name":"Center for Pathobiochemistry and Genetics, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5782-0681","authenticated-orcid":false,"given":"Mario","family":"Mikula","sequence":"additional","affiliation":[{"name":"Center for Pathobiochemistry and Genetics, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.jbspin.2011.05.015","article-title":"Body mass index and susceptibility to knee osteoarthritis: A systematic review and meta-analysis","volume":"79","author":"Jiang","year":"2012","journal-title":"Jt. 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