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The current treatment for early OA is focused on the relief of symptoms, such as pain, but this treatment cannot delay the pathological process. L-Glutamine (L-Gln), which has anti-inflammatory and anti-apoptotic effects, is the most abundant amino acid in human blood. However, its role in OA has not been systematically studied. Therefore, the objective of this work was to explore the therapeutic effect and molecular mechanism of L-Gln on OA. In vitro, we found that L-Gln could up-regulate the expression of the long non-coding RNA NKILA, which is regulated by the transforming growth factor-\u03b21\/SMAD2\/3 pathway, and inhibit the activity of nuclear factor-\u03baB, thereby decreasing the expression of nitric oxide synthase, cyclooxygenase-2, and matrix metalloproteinase-13 (MMP-13). This led to a reduction in the generation of nitrous oxide, prostaglandin E-2, tumour necrosis factor-\u03b1, and degradation of the extracellular matrix (i.e. aggrecan and collagen II) in rat OA chondrocytes. Moreover, intragastric administration of L-Gln reduced the degradation of cartilage tissue and expression of MMP-13 in a rat OA model. L-Gln also relieved the clinical symptoms in some patients with early knee joint OA. These findings highlight that L-Gln is a potential therapeutic drug to delay the occurrence and development of OA.<\/jats:p>","DOI":"10.1042\/cs20220082","type":"journal-article","created":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T10:03:26Z","timestamp":1655892206000},"page":"1053-1069","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["<scp>L-G<\/scp>lutamine alleviates osteoarthritis by regulating lncRNA-<i>NKILA<\/i> expression through the TGF-\u03b21\/SMAD2\/3 signalling pathway"],"prefix":"10.1042","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8370-4131","authenticated-orcid":false,"given":"Xiao","family":"Ma","sequence":"first","affiliation":[{"name":"1Department of Orthopedics, The Second Hospital of Anhui Medical University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dechao","family":"Cai","sequence":"additional","affiliation":[{"name":"1Department of Orthopedics, The Second Hospital of Anhui Medical University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yakun","family":"Zhu","sequence":"additional","affiliation":[{"name":"2Department of Orthopedics, Fuyang Hospital affiliated to Anhui Medical University, Fuyang, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Zhao","sequence":"additional","affiliation":[{"name":"1Department of Orthopedics, The Second Hospital of Anhui Medical University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianbo","family":"Shang","sequence":"additional","affiliation":[{"name":"1Department of Orthopedics, The Second Hospital of Anhui Medical University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"1Department of Orthopedics, The Second Hospital of Anhui Medical University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haotian","family":"Zhang","sequence":"additional","affiliation":[{"name":"1Department of Orthopedics, The Second Hospital of Anhui Medical University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashuai","family":"Bian","sequence":"additional","affiliation":[{"name":"1Department of Orthopedics, The Second Hospital of Anhui Medical University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoran","family":"Yu","sequence":"additional","affiliation":[{"name":"1Department of Orthopedics, The Second Hospital of Anhui Medical University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4182-7202","authenticated-orcid":false,"given":"Wendan","family":"Cheng","sequence":"additional","affiliation":[{"name":"1Department of Orthopedics, The Second Hospital of Anhui Medical University, Hefei, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"key":"2022070608075483100_B1","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1002\/art.39465","article-title":"The prevalence of symptomatic knee osteoarthritis in China: results from the China health and retirement longitudinal study","volume":"68","author":"Tang","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"2022070608075483100_B2","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1016\/S0140-6736(20)30925-9","article-title":"Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019","volume":"396","year":"2020","journal-title":"Lancet"},{"key":"2022070608075483100_B3","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter","year":"2019","journal-title":"Lancet"},{"key":"2022070608075483100_B4","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/s41584-020-00523-9","article-title":"Non-surgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines","volume":"17","author":"Arden","year":"2021","journal-title":"Nat. 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