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Pharmacol."],"abstract":"<jats:p>Osteoarthritis (OA) is a common articular ailment presented with cartilage loss and destruction that is common observed in the elderly population. Physalin A (PA), a natural bioactive withanolide, exerts anti-inflammatory residences in more than a few diseases; however, little is known about its efficacy for OA treatment. Here, we explored the therapeutic effects and potential mechanism of PA in mouse OA. After the <jats:italic>in vitro<\/jats:italic> administration of PA, the expression of inflammation indicators including inducible nitric oxide synthase and cyclooxygenase-2 was low, indicating that PA could alleviate the IL-1\u03b2-induced chondrocyte inflammation response. Moreover, PA reduced IL-1\u03b2-induced destruction of the extracellular matrix by upregulating the gene expression of anabolism factors, including collagen II, aggrecan, and sry-box transcription factor 9, and downregulating the gene expression of catabolic factors, including thrombospondin motif 5 and matrix metalloproteinases. In addition, the chondroprotective effect of PA was credited to the inhibition of mitogen-activated protein kinase (MAPK) and nuclear factor-\u03baB (NF-\u03baB) signaling pathways. Furthermore, <jats:italic>in vivo<\/jats:italic> experiments showed that intra-articular injection of PA could alleviate cartilage destruction in a mouse OA model. However, the anti-inflammatory, anabolism enhancing, catabolism inhibiting, and MAPK and NF-\u03baB signaling pathway inhibiting properties of PA on IL-1\u03b2-induced chondrocytes could be reversed when integrin \u03b1V\u03b23 is knocked down by siRNA. In conclusion, our work demonstrates that PA exhibits a chondroprotective effect that may be mediated by integrin \u03b1V\u03b23. Thus, PA or integrin \u03b1V\u03b23 might be a promising agent or molecular target for the treatment of OA.<\/jats:p>","DOI":"10.3389\/fphar.2021.761922","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:39:10Z","timestamp":1638405550000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Physalin A Inhibits MAPK and NF-\u03baB Signal Transduction Through Integrin \u03b1V\u03b23 and Exerts Chondroprotective Effect"],"prefix":"10.3389","volume":"12","author":[{"given":"Rui","family":"Lu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenggang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-yi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-tao","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junlai","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haokun","family":"Mo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-tao","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An-min","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.joca.2017.10.008","article-title":"Osteoarthritis Year in Review 2017: Biology","volume":"26","author":"Appleton","year":"2018","journal-title":"Osteoarthritis Cartilage"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2684","DOI":"10.4049\/jimmunol.164.5.2684","article-title":"Functional Genomic Analysis in Arthritis-Affected Cartilage: Yin-Yang Regulation of Inflammatory Mediators by Alpha 5 Beta 1 and Alpha V Beta 3 Integrins","volume":"164","author":"Attur","year":"2000","journal-title":"J. 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