{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T06:45:15Z","timestamp":1782715515418,"version":"3.54.5"},"reference-count":46,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T00:00:00Z","timestamp":1781913600000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"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":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Osteoporosis is characterized by excessive bone resorption driven by aberrant osteoclast activation. Solasodine (SOL), a natural steroidal alkaloid, has undefined roles in bone metabolism. This study investigated SOL's effects on RANKL\u2010induced osteoclastogenesis and its underlying mechanisms. Pharmacological targets predicted via network pharmacology and validated by molecular docking identified 81 overlapping targets, which were primarily enriched in MAPK, NF\u2010\u03baB, and JAK\u2013STAT pathways, confirming robust affinity between SOL and core targets including NF\u03baB1, JAK1\/2, and STAT3. In\u00a0vitro, bone marrow\u2010derived macrophages (BMMs) were stimulated with M\u2010CSF and RANKL. Evaluation via TRAcP staining, F\u2010actin immunofluorescence, and hydroxyapatite assays showed that SOL dose\u2010dependently inhibited RANKL\u2010induced osteoclast formation, fusion, and resorptive activity without cytotoxicity. Mechanistic investigations through RT\u2010qPCR, Western blotting, luciferase assays, ROS detection, and live\u2010cell calcium monitoring revealed that SOL suppressed key markers, including NFATc1, c\u2010Fos, CTSK, Atp6v0d2, and Integrin \u03b23. Specifically, SOL attenuated MAPK (p38, JNK, ERK) and STAT3 phosphorylation, inhibited NF\u2010\u03baB activity, and prevented I\u03baB\u2010\u03b1 degradation. Furthermore, SOL curtailed RANKL\u2010induced ROS generation, intracellular calcium oscillations, and subsequent CaMKIV activation. Ultimately, SOL inhibits RANKL\u2010induced osteoclastogenesis and bone resorption by suppressing the NFATc1\/c\u2010Fos axis through coordinated modulation of the MAPK, NF\u2010\u03baB, and JAK\u2013STAT pathways, alongside mitigation of ROS production and calcium signalling, representing a promising natural candidate for treating osteolytic bone diseases.<\/jats:p>","DOI":"10.1111\/jcmm.71253","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T09:20:53Z","timestamp":1781947253000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Solasodine, a Natural Steroidal Alkaloid, Attenuates RANKL\u2010Induced Osteoclastogenesis and Bone Resorption: A Study Based on Network Pharmacology and Experimental Validation"],"prefix":"10.1111","volume":"30","author":[{"given":"Yiwei","family":"Jiang","sequence":"first","affiliation":[{"name":"School of Medicine South China University of Technology  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