{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:19:11Z","timestamp":1790705951725,"version":"4.1.0"},"reference-count":355,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"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":["Medicinal Research Reviews"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Glycogen synthase kinase\u20103 (GSK\u20103) is a central regulator of numerous cellular signaling pathways, with critical roles in metabolism, proliferation, differentiation, and tissue regeneration. This review explores the multifaceted effects of pharmacological GSK\u20103 inhibition across multiple body districts, focusing on its highly context\u2010dependent impact. It has been proven that blocking GSK\u20103 promotes embryonic stem cell self\u2010renewal, neuronal differentiation, osteogenesis, and dentinogenesis, while it has an inhibitory effect on adipogenesis. GSK\u20103 inhibition effects on muscle, heart, liver, and skin are more complex and often contradictory, influenced by critical factors, such as dosage, timing of administration, cellular microenvironment, and isoform specificity (GSK\u20103\u03b1 vs. GSK\u20103\u03b2). A dual role also emerges in fibrosis and epithelial\u2013mesenchymal transition processes, where GSK\u20103 inhibition can either have a suppressive or promoting role. Despite its promising therapeutic potential in regenerative medicine, clinical translation is still hindered by its contradictory effects in some tissues, the need for fine\u2010tuned treatment regimens, and the lack of isoform\u2010specific inhibitors. Selective targeting approaches and robust preclinical studies are thus essential to fully harness the therapeutic potential of GSK\u20103 modulation.<\/jats:p>","DOI":"10.1002\/med.70095","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T10:39:16Z","timestamp":1786012756000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Navigating the Complexity: A Comprehensive Review of GSK\u20103 Inhibition in Regenerative Medicine"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7639-0015","authenticated-orcid":false,"given":"Davide","family":"Schiroli","sequence":"first","affiliation":[{"name":"Transfusion Medicine Unit Azienda USL\u2010IRCCS di Reggio Emilia Reggio Emilia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6291-7872","authenticated-orcid":false,"given":"Alessia","family":"Merra","sequence":"additional","affiliation":[{"name":"The Interdepartmental Center for Stem Cells and Regenerative Medicine (CIDSTEM) University of Modena and Reggio Emilia Reggio Emilia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8053-498X","authenticated-orcid":false,"given":"Chiara","family":"Marraccini","sequence":"additional","affiliation":[{"name":"Transfusion Medicine Unit Azienda USL\u2010IRCCS di Reggio Emilia Reggio Emilia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5712-4272","authenticated-orcid":false,"given":"Lucia","family":"Merolle","sequence":"additional","affiliation":[{"name":"Transfusion Medicine Unit Azienda USL\u2010IRCCS di Reggio Emilia Reggio Emilia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graziella","family":"Pellegrini","sequence":"additional","affiliation":[{"name":"The Interdepartmental Center for Stem Cells and Regenerative Medicine (CIDSTEM) University of Modena and Reggio Emilia Reggio Emilia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8032-6355","authenticated-orcid":false,"given":"Eleonora","family":"Maurizi","sequence":"additional","affiliation":[{"name":"The Interdepartmental Center for Stem Cells and Regenerative Medicine (CIDSTEM) University of Modena and Reggio Emilia Reggio Emilia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3389\/fnmol.2011.00040","article-title":"GSK\u20103: Functional Insights From Cell Biology and Animal Models","volume":"4","author":"Kaidanovich\u2010Beilin O.","year":"2011","journal-title":"Frontiers in Molecular Neuroscience"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/35017574","article-title":"Requirement for Glycogen Synthase Kinase\u20103beta in Cell Survival and NF\u2010kappaB Activation","volume":"406","author":"Hoeflich K. 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