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YTH N6-methyladenosine RNA binding protein 2 mediated m6A modification of circHIPK2 promotes cellular senescence and osteoarthritis progression by inhibiting autophagy - PubMed

4 hours ago
  • #RNA modification
  • #autophagy
  • #osteoarthritis
  • m6A modification of circHIPK2, mediated by YTHDF2, promotes chondrocyte senescence and osteoarthritis progression by inhibiting autophagy.
  • circHIPK2 expression is reduced in human OA cartilage, and its loss exacerbates senescence and impairs autophagy in vitro and in vivo.
  • circHIPK2 interacts with RAB22A; its depletion enhances RAB22A-PI3K association, activating the PI3K-AKT-mTOR pathway and disrupting autophagic flux.
  • Intra-articular delivery of circHIPK2 encapsulated in lipid nanoparticles (circHIPK2-LNP) attenuates chondrocyte senescence and alleviates OA progression in mice.
  • The study identifies circHIPK2 as a potential therapeutic target and prognostic biomarker for cartilage aging in osteoarthritis.