Electroacupuncture on GB acupoints improves osteoporosis via the estradiol-PI3K-Akt signaling pathway

Recent studies have reported that electroacupuncture (EA) can treat osteoporosis, but most of which were based on the "kidney governing bones" theory. However, the ancient Chinese medical textbook Huangdi Neijing pointed out that "Gallbladder Meridian of Foot Shaoyang" correlates with bone diseases, including osteoporosis, although the therapeutic regimens were lost after the Tang Dynasty. Here, we explored whether EA at GB points improves osteoporosis and its underlying mechanism. We constructed ovariectomized mice and treated them with EA at GB30 (Huantiao), GB34 (Yanglingquan), and GB39 (Xuanzhong) acupoints. EA treatment significantly improved bone parameters in osteoporotic mice, as evidenced by micro-computed tomography and histological assessment. Additionally, EA treatment elevated the serum levels of estradiol and SOD that were downregulated in osteoporotic mice. Transcriptome and qPCR results verified that EA treatment upregulated the expression of genes associated with bone formation. Moreover, transcriptome analysis revealed differential enrichment of the PI3K-Akt pathway. Furthermore, Western blot analysis demonstrated that estradiol partially counteracted a reduction in p-AKT expression induced by hydrogen peroxide. These findings indicate that EA treatment increases serum estradiol levels in mice, thus inhibiting osteoporosis induced by oxidative stress. This effect is achieved by activating the PI3K-Akt signaling pathway.