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Reduced molecular weight of hyaluronic acid (HA) in synovial fluid of patients with TMJOA. In addition, high molecular weight hyaluronic acid (HMW\u2010HA) is often used clinically to treat TMJ inflammation. As a pattern recognition receptor of the cytoplasm, ALPK1 was found to be pro\u2010inflammatory in a variety of diseases. However, the relationship of ALPK1, HA and M1 macrophage polarization in TMJ synovitis remains unclear. We aimed to investigate the role of ALPK1 and HA in macrophage polarization and TMJ synovitis and the underlying mechanisms. The results demonstrated that ALPK1 was highly upregulated in the synovial macrophages in the inflamed TMJ synovium of patients. Low molecular weight hyaluronic acid (LMW\u2010HA) promoted the expression of ALPK1 and M1 macrophage\u2010associated genes. Besides, rhALPK1 promoted the expression of M1 macrophage\u2010associated factors and the nuclear translocation of PKM2. Furthermore, ALPK1 knockout mice exhibited limited infiltration of macrophages and decreased expression levels of M1 macrophage\u2010associated genes in CFA\u2010induced TMJ synovitis. While HMW\u2010HA inhibited the expression of ALPK1 and M1 macrophage polarization. Our results elucidated that ALPK1 promoted TMJ synovitis by promoting nuclear PKM2\u2010mediated M1 macrophage polarization, whereas HMW\u2010HA inhibited the expression of ALPK1 as well as M1 macrophage polarization.<\/jats:p>","DOI":"10.1111\/jcmm.18172","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T02:49:05Z","timestamp":1710730145000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The relationship of <scp>ALPK1<\/scp>, hyaluronic acid and <scp>M1<\/scp> macrophage polarization in the temporomandibular joint synovitis"],"prefix":"10.1111","volume":"28","author":[{"given":"Jie","family":"Zhao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Oral and Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School and Hospital of Stomatology Wuhan University  Wuhan 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