Abstract

Osteoarthritis (OA) is a chronic progressive joint disease. In China, bee sting acupuncture (BSA) has been widely used to treat OA. However, the molecular mechanisms underlying the therapeutic effects of BSA against OA remain unexplored. This study aims to further investigate the role and potential mechanism of BSA in treating OA. Live bee stings alternately acupunctured two acupoints, Zusanli (ST36) and Xuehai (SP10) of monosodium iodoacetate-induced OA mice for 6 weeks. BSA treatment alleviated the pathological changes of articular cartilages and reduced serum CTX-II levels in OA mice. Network pharmacology and molecular docking predicted that pro-inflammatory factors, extracellular matrix (ECM) degrading enzymes and apoptosis-related factors could be the key targets of bee venom (BV)’ effects on OA-related diseases. Experimentally, BSA treatment reduced the serum IL-1β and TNF-α levels, and diminished the expression of IL-1β, IL-6, NF-κB, MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, ADAMTS 5, Bax, Caspase 9 and Caspase 3, and increased that of Bcl-2 in knee joints of OA mice. Furthermore, it was confirmed that BSA treatment could activate PPAR-γ in knee joints of OA mice with RNA-seq and Western blot assays. Moreover, BV application significantly increased cell viability and proliferation, and PPAR-γ expression compared with PPAR-γ antagonist GW9662 treatment alone or combined with BV in IL-1β-induced mouse primary chondrocytes. This research revealed that BSA treatment could inhibit NF-κB signaling pathway by activating PPAR-γ, thereby alleviated cartilage inflammation, ECM degradation and apoptosis in OA mice, which provided a basis for BSA therapy in treating OA.