AUTHOR=Ye Jiang-nan , Su Cheng-guo , Jiang Yu-qing , Zhou Yan , Sun Wen-xi , Zheng Xiao-xia , Miao Jin-tao , Li Xiang-yue , Zhu Jun TITLE=Effects of acupuncture on cartilage p38MAPK and mitochondrial pathways in animal model of knee osteoarthritis: A systematic evaluation and meta-analysis JOURNAL=Frontiers in Neuroscience VOLUME=Volume 16 - 2022 YEAR=2023 URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2022.1098311 DOI=10.3389/fnins.2022.1098311 ISSN=1662-453X ABSTRACT=Abstract Background:Most previous studies on acupuncture in the treatment of knee osteoarthritis (KOA) have focused on improving functional efficacy and safety, while related mechanisms have not been systematically reviewed. Acupuncture modulates cytokines to attenuate cartilage extracellular matrix degradation and apoptosis, key to the pathogenesis of KOA, but the mechanisms are complex. Objective:The present study is a meta-analysis which aims to understand the molecular mechanisms by which acupuncture affects p38 mitogen-activated protein kinase (p38MAPK) and mitochondria during cartilage degeneration in KOA and the effect of acupuncture on cartilage-related phenotypes. Methods:Nine databases including Pubmed, Embase, Web of Science (including Medline), Cochrane library, Scopus, CNKI, Wan Fang, and VIP were searched to retrieve animal studies on acupuncture interventions in KOA published since the inception of the journal. Relevant literature was screened, and information extracted. Meta-analysis was performed using Revman 5.4 and Stata 17.0 software. Results:The 40 included studies involved 288 animals, half of which were in acupuncture groups and half in model groups. The mean quality level was 6.8, indicating moderate quality. Meta-analysis showed that acupuncture had the following significant effects on cytokine levels in p38MAPK and mitochondrial pathways: enhanced B cell lymphocytoma-2 (Bcl-2), collagen II, aggrecan expression and significant inhibition of p38MAPK, interleukin-1beta (IL-1β), tumor necrosis factor alpha (TNF-α), phosphorylated (p)-p38MAPK, matrix metalloproteinase-13 (MMP-13), MMP-1, a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMST-5), Bcl-2-associated X protein (Bax), cysteine protease-3 (caspase-3), caspase-9, and Cytochrome-c (Cyt-c) expression. In addition acupuncture significantly reduced chondrocyte apoptosis, Mankin's score (a measure of cartilage damage), and improved cartilage morphometric characteristics. Conclusion:Acupuncture may inhibit cytokine expression in the p38MAPK pathway to attenuate cartilage extracellular matrix degradation, regulate cytokines in the mitochondrial pathway to inhibit chondrocyte apoptosis, and improve cartilage tissue-related phenotypes to delay cartilage degeneration. These findings provide possible explanations for the therapeutic mechanisms and clinical benefits of acupuncture for KOA.