Mechanism of acupoint penetration acupuncture therapy regulating chondrocyte autophagy via the PI3K/Akt-mTOR pathway in KOA rats

Objective:To investigate whether acupoint penetration acupuncture(APA)could regulate chondrocyte autophagy and apoptosis via the PI3K/Akt-mTOR signaling pathway to reduce cartilage degeneration in knee osteoarthritis(KOA)rats.Methods: KOA was induced in rats via intra-articular injection of sodium iodoacetate resolution.Forty male Sprague-Dawley rats were randomly assigned to blank control,model,APA,electro-acupuncture(EA),and sham model groups(n=8)and those in the APA and EA groups received their respective therapies.Following completion of the treatment course,histological examinations of cartilage and muscle were conducted.Levels of apoptosis-and autophagy-related factors,including Bax,Bcl-2,mTOR,ULK-1,and Beclin-1 protein,and mRNAs were assessed.Additionally,β-endorphin(β-EP)concentrations in the brain and serum were measured.Results: Histological analysis revealed that APA alleviated cartilage and muscle damage compared with the model group.APA inhibited cartilage degeneration by modulating the expression of apoptosis-and autophagy-related proteins and mRNA,thus preventing chondrocyte apoptosis.In the APA group,Bax and mTOR protein levels were significantly lower than those in the model group(both P=.024).Conversely,the Bcl-2 expression level was significantly higher than that in the EA group(P=.035).Additionally,ULK-1 expression was significantly lower than that in the EA group(P=.045).The mRNA level of Bax was significantly higher than that in the blank control group(P<.001).However,Beclin-1 levels were significantly higher than those in both the model and EA groups(both P<.001).ELISA results showed a significant decrease in the concentration ofβ-EP in the brains of the rats in the APA group compared with those in the model group(P=.032).Conclusions: APA reduced osteoarthritis-related pain and alleviated cartilage damage by upregulating chondrocyte autophagy and down-regulating apoptosis via signaling pathways involving PI3K/Akt-mTOR in KOA rats.