Acupoint Selection Patterns and Potential Mechanisms of Acupuncture in Knee Osteoarthritis: A Combined Data Mining and Network Pharmacology Study

Objective: To identify the core acupoint prescription and Kellgren-Lawrence (K-L) grade-dependent compatibility patterns of acupuncture for KOA through complex network analysis, and to predict the potential molecular mechanisms underlying the core prescription via network pharmacology. Methods: Literature was retrieved from PubMed, EMbase, Cochrane Library, Web of Science, CNKI, Wanfang, VIP, and SinoMed (inception to September 3, 2025). Frequency, association rule, complex network, and K-L grade subgroup analyses were applied. Potential targets of the core prescription were identified via network pharmacology and intersected with disease targets from OMIM, Therapeutic Target, GeneCards, and DrugBank. A protein-protein interaction (PPI) network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the potential molecular mechanisms. Results: We included 522 studies, yielding 582 prescriptions involving 123 acupoints. The core prescription comprised 24 acupoints, including Dubi (ST35), Neixiyan (EX-LE4), Liangqiu (ST34), Xuehai (SP10), Zusanli (ST36), Yanglingquan (GB34), Yinlingquan (SP9), among others. K-L subgroup analysis revealed ST35, GB34, SP9, and SP10 as universal core acupoints. The mild-to-moderate subgroup mainly used local acupoints, while the moderate-to-severe subgroup centered on ST35, with increased distal acupoint usage and higher degree values. Network pharmacology analysis identified 77 overlapping targets. Core targets included tumor necrosis factor (TNF), interleukin 6 (IL6), interleukin 1 beta (IL1B), tumor protein p53 (TP53), matrix metallopeptidase 9 (MMP9), signal transducer and activator of transcription 3 (STAT3), transforming growth factor beta 1 (TGFB1), caspase 3 (CASP3), and B-cell lymphoma 2 (BCL2), which were enriched in inflammation and immunity, cartilage metabolism, and tissue repair pathways. Conclusion: The core acupoint prescription for KOA features local acupoints combined with distal ones, exhibiting distinct patterns across K-L grades. Our computational findings suggest that core acupoints may potentially delay knee joint degeneration by synergistically regulating inflammation, cartilage metabolism, apoptosis, and tissue repair, although these predictions require experimental validation. These findings provide preliminary evidence and a theoretical basis for standardized clinical point selection and further mechanistic research. Keywords: knee osteoarthritis, KOA, acupuncture, core acupoints, complex network analysis, network pharmacology