摘要
Osteoarthritis(OA)is the most prevalent degenerative joint disease among older adults[1].Given no Food and Drug Administration(FDA)-approved treatments or effective interventions to limit its progression,emerging targets regulating articular cartilage homeostasis and related strategies are warranted for OA therapeutics.OA is an inflammation-related disease.Recent studies have identified pattern recognition receptors(PRRs)as key regulators in auto-inflammatory diseases[2].Protein kinase R(PKR),one PRR,recognizes long double-stranded RNAs(dsRNAs)from viruses or aberrant cellular sources.PKR binding to dsRNAs longer than 33 base pairs(bp)leads to dimerization,autophosphorylation and interferon expression[3].PKR dysregulation is linked to diseases with auto-inflammation and auto-immune features,including systemic lupus erythematosus(SLE)[4],psoriasis[5],Alzheimer’s disease[6,7],and also OA[8].In OA,mitochondrial dsRNAs(mt-dsRNAs)expression and its cytosolic efflux are facilitated in chondrocytes,promoting innate immune activation[8].Mt-dsRNAs are also released into cytosol and extracellular space,where they respectively activate PKR and toll-like receptor 3(TLR3)at the plasma membrane[8].
基金
supported by National Key R&D Program of China(2021YFA1300501 and 2022YFA0806600)
Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0570000)
Science and Technology Commission of Shanghai Municipality(23DX1900100 and 23DX1900101)
the National Natural Science Foundation of China(82202742,82230082,and 81991512)
supported by the New Cornerstone Science Foundation.Ling-Ling Chen is a SANS Senior Investigator.
