黄芩-栀子药对通过调控SphK1介导的糖酵解缓解CIA小鼠骨侵蚀的机制研究OA

This study aims to investigate whether Scutellariae Radix-Gardeniae Fructus(S-G)drug pairs alleviate joint inflammation and bone erosion in collagen-induced arthritis(CIA)mice by regulating sphingosine kinase 1(SphK1)-mediated glycolysis and inhibiting the differentiation of osteoclasts(OCs)induced by receptor activator of nuclear factor-κB ligand(RANKL).Potential therapeutic targets of S-G drug pairs were screened via network pharmacology,followed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment and molecular docking analyses.The effects of S-G drug pairs on bone erosion,inflammatory cytokines,glycolysis-related factors,and OCs differentiation were evaluated using both the CIA mouse model and the RAW264.7 cell in vitro induction system.In vivo results showed that S-G drug pairs alleviated joint swelling and synovial inflammation,reduced OCs number,and modulated the expression of key cytokines,including RANKL,osteoprotegerin(OPG),interleukin(IL)-6,and IL-10.In vitro findings further demonstrated that serum containing the drug significantly inhibited RANKL-induced OCs differentiation,reduced F-actin ring formation,and lowered levels of lactate acid(LA)and lactate dehydrogenase A(LDH-A).Additionally,it suppressed the expression of glycolysis-and bone resorption-related proteins and genes such as SphK1,pyruvate kinase M2(PKM2),oncoprotein c-Myc(c-Myc),and cathepsin K(CTSK),while also weakening the interaction between SphK1 and PKM2.In conclusion,S-G drug pairs could inhibit OCs differentiation by regulating SphK1-mediated glycolytic metabolism,thereby mitigating rheumatoid arthritis-induced bone erosion.