{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:03:40Z","timestamp":1790859820700,"version":"4.1.0"},"reference-count":54,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,21]],"date-time":"2024-04-21T00:00:00Z","timestamp":1713657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundamental Grant","award":["FF-2024-090"],"award-info":[{"award-number":["FF-2024-090"]}]},{"name":"Faculty of Medicine, Universiti Kebangsaan, Malaysia","award":["FF-2024-090"],"award-info":[{"award-number":["FF-2024-090"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Glycogen synthase kinase 3-beta (GSK3\u03b2) is a highly conserved protein kinase originally involved in glucose metabolism, insulin activity, and energy homeostasis. Recent scientific evidence demonstrated the significant role of GSK3\u03b2 in regulating bone remodelling through involvement in multiple signalling networks. Specifically, the inhibition of GSK3\u03b2 enhances the conversion of osteoclast progenitors into mature osteoclasts. GSK3\u03b2 is recognised as a pivotal regulator for the receptor activator of nuclear factor-kappa B (RANK)\/receptor activator of nuclear factor-kappa B ligand (RANKL)\/osteoprotegerin (OPG), phosphatidylinositol-3-kinase (PI3K)\/protein kinase B (AKT), nuclear factor-kappa B (NF-\u03baB), nuclear factor-erythroid 2-related factor 2 (NRF2)\/Kelch-like ECH-associated protein 1 (KEAP1), canonical Wnt\/beta (\u03b2)-catenin, and protein kinase C (PKC) signalling pathways during osteoclastogenesis. Conversely, the inhibition of GSK3\u03b2 has been shown to prevent bone loss in animal models with complex physiology, suggesting that the role of GSK3\u03b2 may be more significant in bone formation than bone resorption. Divergent findings have been reported regarding the efficacy of GSK3\u03b2 inhibitors as bone-protecting agents. Some studies demonstrated that GSK3\u03b2 inhibitors reduced osteoclast formation, while one study indicated an increase in osteoclast formation in RANKL-stimulated bone marrow macrophages (BMMs). Given the discrepancies observed in the accumulated evidence, further research is warranted, particularly regarding the use of GSK3\u03b2 silencing or overexpression models. Such efforts will provide valuable insights into the direct impact of GSK3\u03b2 on osteoclastogenesis and bone resorption.<\/jats:p>","DOI":"10.3390\/biom14040502","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T07:44:09Z","timestamp":1713771849000},"page":"502","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Glycogen Synthase Kinase-3 Beta (GSK3\u03b2) as a Potential Drug Target in Regulating Osteoclastogenesis: An Updated Review on Current Evidence"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1184-4551","authenticated-orcid":false,"given":"Sok Kuan","family":"Wong","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Florencio-Silva, R., Sasso, G.R., Sasso-Cerri, E., Sim\u00f5es, M.J., and Cerri, P.S. 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