[Electroacupuncture alleviates articular chondrocyte apoptosis in rats with knee osteoarthritis by regulating the TLR4/MyD88/NF-κB signaling pathway].

OBJECTIVES

To investigate the effect of electroacupuncture (EA) on chondrocyte apoptosis in rats with knee osteoarthritis (KOA) and the underlying mechanism.

METHODS

Twenty-seven SD rats were randomly divided into blank group, KOA model group, and EA group (n=9). Rat models of KOA were established by intra-articular injection of monosodium iodoacetate, and EA treatment was administered at the acupoints "Neixiyan", "Dubi", "Xuehai", and "Yanglingquan" (dense-sparse wave, 2/100 Hz, 0.5-1.0 mA, 20 min/day for 14 days). Knee function of the rats was assessed using Lequesne MG scale, and cartilage pathologies and ultrastructural changes were observed with HE staining and transmission electron microscopy. The protein expressions of TLR4, MyD88, NF-κB p65, COL2, COL10, Bax, Bcl-2, and caspase-3 and mRNA levels of TLR4, MyD88, and NF‑κB p65 were detected using Western blotting and RT-qPCR; serum levels of IL-1β and TNF‑α were determined with ELISA. Another 15 rats were randomized into blank control, model, TLR4 inhibitor (TAK-242), EA, and sham-EA groups (n=3) for analysis of HMGB1 and key pathway protein expressions and NF‑κB p65 nuclear translocation.

RESULTS

The KOA rats showed increased Lequesne MG scores, obvious chondrocyte injuries, upregulated TLR4, MyD88, NF‑κB p65, COL10, Bax, and caspase-3 expressions, increased serum IL-1β and TNF‑α levels with decreased COL2 and Bcl-2 expressions. EA significantly reduced Lequesne MG scores, improved cartilage pathologies and reversed the abnormal changes in protein expressions and inflammatory cytokines. The KOA rats showed increased HMGB1 expression and enhanced NF‑κB p65 nuclear translocation, and EA treatment effectively decreased HMGB1 expression, reduced nuclear NF‑κB p65, and increased cytoplasmic NF‑κB p65. The TLR4 inhibitor produced similar effects, while sham EA produced no significant effect.

CONCLUSIONS

EA alleviates cartilage injury in KOA rats possibly by inhibiting HMGB1-mediated activation of TLR4/MyD88/NF‑κB signaling and NF‑κB p65 nuclear translocation to regulate Bcl-2/Bax balance and suppress mitochondria-dependent chondrocyte apoptosis.