ALKBH5 Regulates Apoptosis of Rheumatoid Arthritis Fibroblast-like Synoviocytes by Modulating miR-181b-5p Maturation via m6A Demethylation

IntroductionRheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation, joint destruction, and a range of systemic complications.The pathogenesis of RA is multifactorial, involving genetic, epigenetic, and environmental components 2 .Clinically, patients often present with morning stiffness, joint swelling, and pain 3 .If left untreated, RA can result in irreversible joint deformities, functional disability, and serious systemic manifestations, including cardiovascular complications 4 .Despite significant advances in therapeutic strategies, a substantial proportion of patients continue to experience persistent disease activity.Fibroblast-like synoviocytes (FLS) are central to RA pathogenesis.Their aberrant behavior plays a key role in sustaining chronic inflammation and promoting joint destruction 5,6 .In RA, FLS acquire tumor-like features, including uncontrolled proliferation, resistance to apoptosis, and elevated secretion of pro-inflammatory cytokines 7 .These pathological traits contribute to synovial hyperplasia and the release of matrix-degrading enzymes, accelerating cartilage and bone erosion 8 .Although the involvement of FLS in RA has been well established, targeted therapies specifically aimed at correcting their dysfunctional behavior remain limited 9 .ALKBH5, a member of the AlkB family of Fe(II)/ketoglutarate-dependent dioxygenases, functions as an RNA demethylase that removes N6-methyladenosine (m6A) modifications.It plays a pivotal role in the posttranscriptional regulation of gene expression by influencing