{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T06:28:05Z","timestamp":1794032885180,"version":"4.8.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T00:00:00Z","timestamp":1679270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> Synovitis and fibrosis are common pathological features of knee osteoarthritis (KOA). The interaction of synovitis and fibrosis can promote KOA progression. Chrysin (CHR), a natural flavonoid, may treat inflammation and prevent fibrosis. However, the effect and mechanism of CHR in KOA synovitis and fibrosis remains unclear.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The KOA model was established in male SD rats by anterior cruciate ligament transection (ACLT), and histological analysis was used to evaluate synovitis and fibrosis. IL-6, IL-1\u03b2 and TNF-\u03b1 mRNA expression in synovial tissue was measured by qRT\u2012PCR. Immunohistochemistry (IHC) was performed to detect GRP78, ATF-6 and TXNIP expression in vivo. Synovial fibroblasts (SFs) were treated with TGF-\u03b21 to stimulate the inflammatory response and fibrosis. CCK-8 assays were used to detect the viability of CHR-treated SFs. The IL-1\u03b2 level was detected by immunofluorescence analysis. Coimmunoprecipitation (Co-IP) and double immunofluorescence colocalization were used to detect the physiological interaction between TXNIP and NLRP3. The expression of fibrosis-related mediators and PERK\/TXNIP\/NLRP3 signaling molecules was detected by western blotting and qRT-PCR.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Four weeks after CHR treatment, pathological sections and associated scores showed that CHR improved synovitis and fibrosis in the ACLT model. In vitro, CHR attenuated the TGF-\u03b21-induced inflammatory response and fibrosis in SFs. Moreover, CHR suppressed the expression of synovial fibrosis markers and PERK\/TXNIP\/NLRP3 signaling molecules in the synovial tissue of rats with ACLT and cultured SFs. More importantly, we found that CHR inhibited TXNIP-NLRP3 interactions in TGF-\u03b2-induced SFs.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Our findings indicate that CHR can ameliorate synovitis and fibrosis in KOA. The underlying mechanism may be related to the PERK\/TXNIP\/NLRP3 signaling pathway.<\/jats:p>","DOI":"10.3389\/fphar.2023.1170243","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T05:00:40Z","timestamp":1679288440000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":39,"title":["Chrysin ameliorates synovitis and fibrosis of osteoarthritic fibroblast-like synoviocytes in rats through PERK\/TXNIP\/NLRP3 signaling"],"prefix":"10.3389","volume":"14","author":[{"given":"Liang","family":"Ding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiyang","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yibao","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runlin","family":"Xing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peimin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1111\/wrr.12939","article-title":"Fibroblast-like synoviocytes: Role in synovial fibrosis associated with osteoarthritis","volume":"29","author":"Maglaviceanu","year":"2021","journal-title":"Wound Repair Regen"},{"key":"B2","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1002\/path.4738","article-title":"Grp78 and chop modulate macrophage apoptosis and the development of bleomycin-induced pulmonary fibrosis","volume":"239","author":"Ayaub","year":"2016","journal-title":"J. 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