IL-17A exacerbates synovial inflammation in osteoarthritis via activation of endoplasmic reticulum stress

The primary clinical manifestations of osteoarthritis (OA) are joint pain and restricted movement capabilities. Synovial inflammation, serving as an initiator of OA progression, intensifies cartilage damage via the generation of various deleterious agents, including pro-inflammatory cytokines and nociceptive mediators. Despite extensive research on modulating synovial inflammation to retard OA progression, the underlying pathophysiological mechanisms of synovial inflammation in OA remain elusive. Interleukin-17A (IL-17A), a pro-inflammatory cytokine released by activated T lymphocytes, is a therapeutic target for numerous inflammatory and autoimmune pathologies. This study investigates the role and mechanism of IL-17A in OA synovial inflammation using both in vivo and in vitro models and examines the impact of the endoplasmic reticulum stress (ERS) inhibitor, 4-Phenylbutyric Acid (4-PBA). Our findings indicate that IL-17A may be implicated in synovial inflammation through ERS and suggest a potential therapeutic direction for mitigating synovial inflammation in OA.