The relationship of ALPK1, hyaluronic acid and M1 macrophage polarization in the temporomandibular joint synovitis

Abstract M1 macrophage polarization and synovitis play an important role in the pathogenesis of temporomandibular joint osteoarthritis (TMJOA). Reduced molecular weight of hyaluronic acid (HA) in synovial fluid of patients with TMJOA. In addition, high molecular weight hyaluronic acid (HMW‐HA) is often used clinically to treat TMJ inflammation. As a pattern recognition receptor of the cytoplasm, ALPK1 was found to be pro‐inflammatory 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‐HA) promoted the expression of ALPK1 and M1 macrophage‐associated genes. Besides, rhALPK1 promoted the expression of M1 macrophage‐associated factors and the nuclear translocation of PKM2. Furthermore, ALPK1 knockout mice exhibited limited infiltration of macrophages and decreased expression levels of M1 macrophage‐associated genes in CFA‐induced TMJ synovitis. While HMW‐HA inhibited the expression of ALPK1 and M1 macrophage polarization. Our results elucidated that ALPK1 promoted TMJ synovitis by promoting nuclear PKM2‐mediated M1 macrophage polarization, whereas HMW‐HA inhibited the expression of ALPK1 as well as M1 macrophage polarization.