Neuregulin 4 inhibits synovial macrophage pro-inflammatory polarization via ErbB4/Stat5b/NF-κB signaling to alleviate osteoarthritis progression.

ABSTRACT: Osteoarthritis (OA) is a chronic inflammatory disease characterized by synovial inflammation and cartilage degradation. Synovial macrophages, as a key driver of OA progression, during all stages of OA and induced to produce inflammatory cytokines that aggravate the degradation of cartilage. Here, we demonstrate that neuregulin-4 (Nrg4) deficiency exacerbates synovial pro-inflammatory macrophage transformation and articular cartilage abrasion in a mouse model of OA. Conversely, Nrg4 re-expression significantly reduces pro-inflammatory macrophage accumulation and synovial inflammation, thereby attenuating OA progression. Mechanistically, Nrg4 activates the ErbB4/Stat5b signaling pathway, which subsequently suppresses NF-κB activation, leading to reduced pro-inflammatory macrophage transforma

SUBMITTER: Jiang D 

PROVIDER: S-EPMC12465901 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature