{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T17:05:40Z","timestamp":1792256740258,"version":"4.4.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T00:00:00Z","timestamp":1724889600000},"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>Osteoarthritis (OA) is the most prevalent cartilage degenerative and low-grade inflammatory disease of the whole joint. However, there are currently no FDA-approved drugs or global regulatory agency-approved treatments OA disease modification. Therefore, it\u2019s essential to explore novel effective therapeutic strategies for OA. In our study, we investigated the effects of AFK-PD, a novel pyridone agent, on the development of OA induced by destabilization of the medial meniscus (DMM) <jats:italic>in vivo<\/jats:italic>, and its impact on the function of chondrocytes treated with IL-1\u03b2 <jats:italic>in vitro<\/jats:italic>. Our results demonstrated AFK-PD alleviated OA progression through inhibiting cartilage degeneration, articular inflammation and osteophyte formation. Notably, AFK-PD inhibited chondrocyte inflammation and synovial macrophage M1 polarization, leading to the attenuation of articular inflammation. Additionally, AFK-PD promoted chondrocyte anabolism while mitigating catabolism and apoptosis, effectively inhibiting cartilage degeneration. Mechanistically, AFK-PD suppressed the expression of key signaling molecules involved in the MAPK pathway, such as p-ERK1\/2 and p-JNK, as well as the NF-\u03baB signaling molecule p-p65, in IL-1\u03b2-induced chondrocytes. These findings suggest AFK-PD ameliorates the development of OA by protecting chondrocyte functions and inhibiting articular inflammation in chondrocytes and synovial macrophages. Overall, our study highlights AFK-PD as a promising therapeutic candidate for the treatment of OA.<\/jats:p>","DOI":"10.3389\/fphar.2024.1439678","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T05:07:01Z","timestamp":1724908021000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["AFK-PD alleviated osteoarthritis progression by chondroprotective and anti-inflammatory activity"],"prefix":"10.3389","volume":"15","author":[{"given":"Zhuang","family":"Qian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenlin","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueqiang","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohua","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"21592","DOI":"10.1073\/pnas.1908981116","article-title":"L-type voltage-gated Ca(2+) channel CaV1.2 regulates chondrogenesis during limb development","volume":"116","author":"Atsuta","year":"2019","journal-title":"Proc. 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