Effects of Electroacupuncture on Knee Osteoarthritis in Rats Through Suppressing p38 MAPK/ERK/CREB Pathway

Knee osteoarthritis (KOA) is a chronic degenerative joint disease and recognized as the fourth leading cause of disability worldwide. Despite the proven clinical efficacy of electroacupuncture (EA) in alleviating KOA-related symptoms, the precise molecular mechanisms underlying its therapeutic effects remain incompletely elucidated. The purpose of this study is to determine and validate the potential therapeutic targets and mechanism of EA for KOA through a combined approach of in vivo experiments and transcriptomics analysis.

A total of 40 SD rats were randomly divided into four groups: control group, model group, two-course EA intervention group, and four-course EA treatment group. The KOA model was established with monosodium iodoacetate (MIA) intra-articular injection. The EA treatment groups received intervention at the Yanglingquan and Dubi acupoints. The control group received no intervention. All four groups underwent behavioral assessments (rat knee joint diameter and bilateral foot balance test), joint pathological analysis (Micro-CT and hematoxylin and eosin staining) to evaluate the effect of EA on KOA. Transcriptomics, GO analysis and KEGG analysis were applied to predict potential targets. Potential targets were further verified via Western blot (WB).

EA could significantly reduce knee joint diameters and improve the supporting force of KOA rats. Micro-CT revealed that EA increased the subchondral bone mass of KOA rats. ELISA results suggest that the levels of interleukin-1β and tumor necrosis factor-α decreased after EA intervention. The transcriptomics analysis revealed that EA could downregulate the levels of phospho (p)-p38 mitogen-activated protein kinase (MAPK), p-extracellular signal-regulated kinase (ERK), and p-cAMP response element-binding protein (CREB) which is further verified via WB.

EA intervention significantly ameliorated KOA-induced degeneration of cartilage and subchondral bone, improved pain-associated behavioral performance, alleviated inflammation. The molecular mechanism is related to the inhibition of the p-p38 MAPK/ERK/CREB pathway.