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In this study, we utilized tumor necrosis factor \u03b1 (TNF\u03b1) to establish in vitro OA models and analyzed the effects of dehydrocorydaline (DHC) on cell proliferation and extracellular matrix (ECM) synthesis in human chondrocytes with TNF\u03b1 treatment. We found that TNF\u03b1 treatment significantly reduced cell proliferation and mRNA and protein expression levels of aggrecan and type II collagen, but caused an increase in mRNA and protein expression levels of type I collagen, matrix metalloproteinase 1\/13 (MMP1\/13), and prostaglandin-endoperoxide synthase 2 (PTGS2, also known as Cox2) in human chondrocytes. DHC significantly promoted the cell activity of normal human chondrocytes without showing cytotoxity. Moreover, 10 and 20 \u03bcM DHC clearly restored cell proliferation, inhibited mRNA and protein expression levels of type I collagen, MMP 1\/13, and Cox2, and further increased those of aggrecan and type II collagen in the TNF\u03b1-treated human chondrocytes. RNA transcriptome sequencing indicated that DHC could improve TNF\u03b1-induced metabolic abnormalities and inflammation reactions and inhibit the expression of TNF\u03b1-induced inflammatory factors. Furthermore, we found that the JAK1-STAT3 signaling pathway was confirmed to be involved in the regulatory effects of DHC on cell proliferation and ECM metabolism of the TNF\u03b1-treated human chondrocytes. Lastly, to explore the effects of DHC in vivo, we established an anterior cruciate ligament transection (ACLT)-stimulated rat OA model and found that DHC administration significantly attenuated OA development, inhibited the enzymatic hydrolysis of ECM, and reduced phosphorylated JAK1 and STAT3 protein expression in vivo after ACLT for 6 weeks. These results suggest that DHC can effectively relieve OA progression, and it has a potential to be utilized for the clinical prevention and therapy of OA as a natural small molecular drug.<\/jats:p>","DOI":"10.3390\/ijms23137268","type":"journal-article","created":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:21:50Z","timestamp":1656634910000},"page":"7268","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Dehydrocorydaline Accelerates Cell Proliferation and Extracellular Matrix Synthesis of TNF\u03b1-Treated Human Chondrocytes by Targeting Cox2 through JAK1-STAT3 Signaling Pathway"],"prefix":"10.3390","volume":"23","author":[{"given":"Yongqiang","family":"Sha","sequence":"first","affiliation":[{"name":"Center for Precision Medicine, School of Medicine and School of Biomedical Sciences, Huaqiao University, Xiamen 361021, China"},{"name":"National Innovation and Attracting Talent \u201c111\u201d Base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beibei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Precision Medicine, School of Medicine and School of Biomedical Sciences, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Precision Medicine, School of Medicine and School of Biomedical Sciences, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8891-1797","authenticated-orcid":false,"given":"Chunli","family":"Wang","sequence":"additional","affiliation":[{"name":"National Innovation and Attracting Talent \u201c111\u201d Base, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Sun","sequence":"additional","affiliation":[{"name":"Center for Precision Medicine, School of Medicine and School of Biomedical Sciences, Huaqiao University, Xiamen 361021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.triboint.2014.04.025","article-title":"Designing prosthetic knee joints with bio-inspired bearing surfaces","volume":"77","author":"Qiu","year":"2014","journal-title":"Tribol. 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