Electroacupuncture inhibits the nuclear factor kappa B signaling pathway and alleviates knee synovial membrane inflammation and chondrocyte apoptosis in a rat model of knee osteoarthritis

OBJECTIVES: Knee osteoarthritis (KOA) is a degenerative joint disease that is characterized by cartilage degeneration and inflammation. According to reports, electroacupuncture (EA) can delay joint cartilage degeneration and inhibit inflammation, but its specific mechanisms remain unclear. The objective of this study was to examine the mechanisms through which EA potentially improves cartilage degeneration and inhibits inflammation in KOA. METHODS: In this study, we used monosodium iodoacetate injections to establish a rat KOA model and then performed EA. Cartilage morphology and chondrocyte apoptosis were assessed by hematoxylin-eosin (HE) staining, transmission electron microscopy and scanning electron microscopy. Levels of inflammatory mediators in the synovial membrane were measured by enzyme-linked immunosorbent assay (ELISA). Expression of apoptotic factors in cartilage was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Nuclear factor (NF)-κB pathway components were evaluated by immunofluorescence. To validate the mechanistic role of NFκB signaling, KOA rats were transfected with a NFκB-overexpressing lentivirus, and the effects of EA on phosphorylated (p)-p65, p-IκBα (inhibitor of NFκB), synovial inflammatory factors and cartilage apoptotic markers were examined. RESULTS: HE staining, transmission electron microscopy and scanning electron microscopy showed that EA alleviated chondrocyte apoptosis in our rat model of KOA. ELISA results showed that EA significantly inhibited the expression of inflammatory factors (tumor necrosis factor (TNF)-α, matrix metalloproteinase (MMP)-13, and interleukin (IL)-6) and promoted the expression of the anti-inflammatory factor IL-10 in the synovial membrane. RT-qPCR and Western blotting results showed that EA significantly decreased the expression of apoptotic factors, including the B-cell lymphoma (Bcl-2)-associated X protein (Bax)/Bcl-2 ratio, caspase-3, caspase-8 and caspase-9 in cartilage. Immunofluorescence results showed that EA regulated the NFκB inhibitor protein IκBα and inhibited NFκB p65. In addition, after KOA rats were transfected with an overexpressing NFκB lentivirus, p-p65 expression was significantly upregulated, p-IκBα expression was significantly decreased, and the expression of pro-inflammatory factors in the synovial membrane and apoptosis-related factors in cartilage were significantly upregulated. After EA, p-p65 expression was significantly decreased, p-IκBα expression was significantly upregulated, and the expression of pro-inflammatory factors in the synovial membrane and apoptosis-related factors in cartilage decreased. CONCLUSION: EA decreased synovial inflammation and chondrocyte apoptosis, thereby alleviating cartilage degeneration in a rat model of KOA. EA reversed NFκB signaling pathway activation after NFκB lentivirus transfection, showing that inhibition of synovial inflammation and chondrocyte apoptosis and alleviation of cartilage degeneration by EA are associated with inhibition of NFκB signaling pathway activation.