Electroacupuncture alleviates osteoarthritis and is associated with activation of the Nrf2/HO-1 pathway and reduced ferroptosis-related changes

Background Electroacupuncture (EA) has shown beneficial effects in osteoarthritis (OA), but the underlying mechanism remains unclear. This study examined whether the effects of EA on OA are associated with changes in ferroptosis-related markers and Nrf2/HO-1 signaling. Methods Rats were randomly assigned to the Control, OA, OA + ferrostatin-1, OA + EA, and OA + ferrostatin-1+EA groups. Gross cartilage appearance, paw withdrawal threshold, body weight, and knee joint width were evaluated. Cartilage injury was assessed by HE staining, Safranin O-fast green staining, and OARSI scoring. Inflammatory cytokines in serum and synovial fluid were measured by ELISA. TUNEL staining, immunofluorescence, biochemical assays, and western blot were used to assess apoptosis, ferroptosis-related markers, and Nrf2/HO-1 signaling in cartilage tissue. Results Compared with the Control group, OA rats showed obvious cartilage damage, lower paw withdrawal threshold, reduced body weight gain, and increased knee joint width. Histological injury and OARSI scores were markedly increased in the OA group. Serum and synovial fluid levels of IL-6, IL-1β, and TNF-α were also elevated. In cartilage tissue, OA was associated with increased apoptosis, decreased SLC7A11, GPX4, SOX9, and GSH levels, and increased Fe 2+ and ACSL4 levels. Nrf2 and HO-1 expression was increased in OA cartilage. Treatment with ferrostatin-1, EA, or the combined treatment alleviated these changes to different degrees. Conclusion EA alleviated OA-related structural and inflammatory changes and was associated with reduced ferroptosis-related alterations and enhanced Nrf2/HO-1 signaling.