VEGFA and rheumatoid arthritis: In synovial fibroblasts, Metrnl down-regulates key inflammatory cytokines (IL-6, TNF-α, IL-17) and angiogenic mediators (PDGF, VEGF), thereby disrupting the self-amplifying inflammatory loop of RA that involves IL-6-mediated immune activation, TNF-α-induced synovial destruction, and IL-17-driven osteoclastogenesis [19, 29–33].