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This study aimed to determine the molecular mechanism underlying the effect of clusterin (CLU), anti\u2010apoptotic molecule, in human knee OA chondrocytes. Primary knee OA chondrocytes were isolated from the cartilage of knee OA patients and divided into five groups: (1) the cells treated with interleukin (IL)\u20101\u03b2, (2) CLU alone, (3) a combination of IL\u20101\u03b2 and CLU, (4) LY294002 (PI3K inhibitor) along with IL\u20101\u03b2 and CLU, and (5) the untreated cells. Production of apoptotic, inflammatory, anabolic, and catabolic mediators in knee OA chondrocytes was determined after treatment for 24\u2009h. Our <jats:italic>in<\/jats:italic> <jats:italic>vitro<\/jats:italic> study uncovered that CLU significantly suppressed the production of inflammatory mediators [nitric oxide (NO), IL6, and tumor necrosis factor (TNF)\u2010\u03b1] and apoptotic molecule (caspase\u20103, CASP3). CLU significantly upregulated messenger ribonucleic acid (mRNA) expressions of anabolic factors [SRY\u2010box transcription factor\u20109 (<jats:italic>SOX9<\/jats:italic>) and aggrecan (<jats:italic>ACAN<\/jats:italic>)], but significantly downregulated mRNA expressions of <jats:italic>IL6<\/jats:italic>, nuclear factor kappa\u2010B (<jats:italic>NF\u2010\u03baB<\/jats:italic>), <jats:italic>CASP3<\/jats:italic>, and matrix metalloproteinase\u201013 (<jats:italic>MMP13<\/jats:italic>). Anti\u2010apoptotic and anti\u2010inflammatory effects of CLU were mediated through activating PI3K\/Akt signaling pathway. The findings suggest that CLU might have beneficial effects on knee OA chondrocytes by exerting anti\u2010apoptotic and anti\u2010inflammatory functions via PI3K\/Akt pathway, making CLU a promising target for potential therapeutic interventions in knee OA.<\/jats:p>","DOI":"10.1111\/cts.13881","type":"journal-article","created":{"date-parts":[[2024,7,10]],"date-time":"2024-07-10T04:25:41Z","timestamp":1720585541000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Protective effect of clusterin against interleukin\u20101\u03b2\u2010induced apoptosis and inflammation in human knee osteoarthritis chondrocytes"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5890-932X","authenticated-orcid":false,"given":"Tachatra","family":"Ungsudechachai","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy Mahidol University  Bangkok 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