Kaifang Yao,1,* Md Forhad Shamim,1,* Jiaqi Xia,1 Tingting Tingting Liu,1 Yi Guo,1– 3 Xiaowei Lin1– 3 

1Research Center of Experimental Acupuncture Science, School of Acupuncture & Moxibustion and Tuina, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People’s Republic of China; 2Tianjin Key Laboratory of Modern Chinese Medicine Theory of Innovation and Application, School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 3National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, 301617, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yi Guo, School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 10 Poyang Lake Road, Tuanbo New Town, Jinghai District, Tianjin, 301617, People’s Republic of China, Tel +86-22-2748-5189, Email guoyi_168@163.com Xiaowei Lin, School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 10 Poyang Lake Road, Tuanbo New Town, Jinghai District, Tianjin, 301617, People’s Republic of China, Tel +86-22-2748-5189, Email linxiaoweiwqhz@163.com

Abstract: Knee osteoarthritis (KOA) is a prevalent degenerative joint disorder that significantly compromises joint function due to the progressive degradation of cartilage and persistent inflammation. Acupuncture is an effective technique that has been employed in Traditional Chinese Medicine to treat KOA. This review aims to summarize 21 randomized controlled trials (RCTs) and mechanistic research to investigate acupuncture’s clinical efficacy and biological mechanisms in KOA. The literature was sourced from various databases, including PubMed, CNKI, and Google Scholar. Clinical data revealed that acupuncture monotherapy significantly reduces pain intensity (Visual Analogue Scale reductions: 32– 54%) and enhances functional capacity (WOMAC score improvements: 25– 40%). Furthermore, the combination of acupuncture with moxibustion or electroacupuncture induced synergistic improvements. Mechanistically, acupuncture modulates KOA pathophysiology by suppressing NF-κB-mediated pro-inflammatory cytokines, inhibiting chondrocyte apoptosis (caspase-3 downregulation) while activating autophagy (LC3-II/Beclin-1 upregulation), rebalancing cartilage metabolism by increasing aggrecan/COL2A1 synthesis and MMP-13 inhibition, as well as by attenuating pain transmission through μ-opioid receptor activation and central descending inhibition. These multimodal interventions position acupuncture as a dual-target treatment, mitigating symptoms while inhibiting structural degradation. However, despite promising evidence, further research is warranted for protocol standardization and long-term outcome validation. This review highlights acupuncture’s scientific legitimacy as a non-pharmacological approach for the integrated management of KOA, combining traditional methods with modern mechanistic insights.

Keywords: acupuncture, electroacupuncture, knee osteoarthritis, knee osteoarthritis mechanism, Traditional Chinese Medicine