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Bee sting acupuncture mitigates osteoarthritis in male mice via PPAR-γ activation: integrated network pharmacology,
Zhiyuan Feng1, Jiali Yang2, Ya Zhu1
1College of Bee Science and Biomedicine, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
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.
Insights
Bee sting acupuncture (BSA) effectively treats osteoarthritis (OA) by reducing inflammation and cartilage damage. This study reveals BSA activates PPAR-γ, inhibiting the NF-κB pathway to alleviate OA progression in mice.
Area of Science:
- Orthopedics
- Immunology
- Pharmacology
Background:
- Osteoarthritis (OA) is a prevalent chronic joint disease.
- Bee sting acupuncture (BSA) is a common traditional Chinese medicine treatment for OA.
- The precise molecular mechanisms of BSA's therapeutic effects on OA are not fully understood.
Purpose of the Study:
- To investigate the therapeutic role and underlying molecular mechanisms of BSA in a mouse model of OA.
- To explore the effects of bee venom (BV) on key molecular targets involved in OA pathogenesis.
Main Methods:
- Monosodium iodoacetate-induced OA mice were treated with BSA for six weeks.
- Network pharmacology and molecular docking were used for target prediction.
- Serum cytokine levels, gene/protein expression in knee joints, and chondrocyte responses were analyzed using biochemical assays, RNA-seq, and Western blotting.
Main Results:
- BSA treatment ameliorated cartilage damage and reduced serum CTX-II levels in OA mice.
- BSA significantly decreased pro-inflammatory cytokines (IL-1β, TNF-α) and ECM-degrading enzymes (MMPs, ADAMTS5).
- BSA activated PPAR-γ, inhibited NF-κB signaling, reduced apoptosis, and enhanced chondrocyte viability.
Conclusions:
- BSA effectively alleviates OA by inhibiting the NF-κB pathway through PPAR-γ activation.
- This mechanism reduces cartilage inflammation, ECM degradation, and apoptosis in OA.
- The findings provide a scientific basis for BSA as a therapeutic strategy for osteoarthritis.
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