{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T15:07:27Z","timestamp":1779289647568,"version":"3.51.4"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Knee osteoarthritis (KOA) is a degenerative joint disease commonly seen in middle\u2010aged and elderly individuals. With the increasing aging population, the incidence of KOA has been rising annually, yet there remains no definitive cure. Studies have shown that scoparone exhibits potent anti\u2010inflammatory effects in treating inflammatory diseases, but its specific mechanism in KOA remains unclear. Network pharmacology was employed to systematically predict the putative therapeutic targets and signaling pathways of scoparone against KOA. The resulting candidate genes and pathways were subsequently examined by molecular docking and then experimentally verified in a well\u2010established KOA mouse model. ELISA, HE staining, immunohistochemical staining, and western blot were used to detect the expression of related factors. Network pharmacology analysis initially identified 15 intersecting target genes of scoparone in the treatment of KOA. These target genes were primarily enriched in 46 signaling pathways, with the most significant involvement in focal adhesion, Ras\u2010related protein 1 (RAP1) signaling pathway, high\u2010affinity IgE Fc receptor (Fc\u03b5RI) signaling pathway. Molecular docking results revealed that prostaglandin\u2010endoperoxide synthase 2 (PTGS2), insulin\u2010like growth factor 1 receptor (IGF1R), and cathepsin K (CTSK) exhibited the highest binding affinity with scoparone. Animal experiments demonstrated that scoparone reversed the abnormal expression of PTGS2, IGF1R, and CTSK in the knee cartilage of KOA mice. Additionally, scoparone suppressed inflammation and extracellular matrix degradation in KOA mice by modulating the RAP1 signaling pathway and the Fc\u03b5RI\/spleen tyrosine kinase (Syk) signaling pathway. These findings provide a critical theoretical foundation for further research and development of scoparone in the treatment of KOA.<\/jats:p>","DOI":"10.1002\/jor.70162","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T05:33:22Z","timestamp":1771392802000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanism of Scoparone Against Knee Osteoarthritis: A Study Integrating Network Pharmacology, Animal Experiments, and Molecular Docking"],"prefix":"10.1002","volume":"44","author":[{"given":"Linshuai","family":"Shi","sequence":"first","affiliation":[{"name":"Department of Orthopedics The 988th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army Zhengzhou Henan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The 988th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army Zhengzhou Henan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinqi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The 988th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army Zhengzhou Henan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The 988th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army Zhengzhou Henan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3533-7584","authenticated-orcid":false,"given":"Ke","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The 988th Hospital of the Joint Logistics Support Force of the Chinese People's Liberation Army Zhengzhou Henan 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