Isoquercitrin ameliorates chondrocyte dysfunction in osteoarthritis by targeting AKT1-mediated mitochondrial dynamics regulation

Yuan Ding, Xiang Wang, Shihua Zong, Qiong Wen and Luyang Zhang

PLOS ONE, 2026, vol. 21, issue 9, 1-23

Abstract: Osteoarthritis (OA), a prevalent degenerative joint disorder, is driven by chondrocyte anabolic-catabolic imbalance, aberrant inflammation, and mitochondrial dysfunction. Disease-modifying therapies targeting these pathological processes remain scarce, limiting effective clinical intervention. Herein, we demonstrate an isoquercitrin (IQ)-based chondroprotective strategy that rectifies osteoarthritis-related chondrocyte impairment by targeting AKT1. IQ first reverses IL-1β-induced chondrocyte proliferation arrest, shifts metabolic homeostasis toward anabolism, and mitigates pro-inflammatory responses. It simultaneously restores mitochondrial homeostasis by normalizing dynamic balance. Mechanistically, IQ binds to AKT1 with high affinity, and AKT1 overexpression abolishes its protective effects—confirming AKT1 as a key mediator. This approach re-establishes chondrocyte functional homeostasis by coupling anti-inflammatory, metabolic-regulatory, and mitochondrial-stabilizing activities. This work highlights IQ as a promising candidate for osteoarthritis intervention and provides a mechanistic framework linking AKT1 targeting to chondroprotection.

Date: 2026
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Persistent link: https://EconPapers.repec.org/RePEc:plo:pone00:0357989

DOI: 10.1371/journal.pone.0357989

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