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The Wnt signalling pathway, a key regulator of bone maintenance, remains partially understood in osteoporosis. Our research delves into the role of Wnt\u2010related molecules in this disease. In osteoporotic adipose\u2010derived stem cells (OP\u2010ASCs), we detected a significant decrease in <jats:italic>Ctnnb1<\/jats:italic> and <jats:italic>Frizzled\u20106<\/jats:italic> (<jats:italic>Fzd6<\/jats:italic>), contrasted by an increase in <jats:italic>Gsk\u20103\u03b2<\/jats:italic> and <jats:italic>Wnt5a<\/jats:italic>. Activation of the Wnt pathway by LiCl resulted in elevated <jats:italic>Ctnnb1<\/jats:italic> and <jats:italic>Fzd6<\/jats:italic>, but decreased <jats:italic>Gsk\u20103\u03b2<\/jats:italic> and <jats:italic>Wnt5a<\/jats:italic> levels, promoting OP\u2010ASCs' bone\u2010formation capacity. In contrast, inhibition of this pathway by DKK\u20101 led to diminished <jats:italic>Ctnnb1<\/jats:italic> and <jats:italic>Fzd6<\/jats:italic>, and increased <jats:italic>Gsk\u20103\u03b2<\/jats:italic> and <jats:italic>Wnt5a<\/jats:italic>, adversely affecting osteogenesis. Furthermore, our findings show that overexpressing <jats:italic>Wnt5a<\/jats:italic> impedes, while silencing it enhances the bone\u2010forming capability of OP\u2010ASCs. In a cranial bone defect model, the implantation of <jats:italic>Wnt5a<\/jats:italic>\u2010silenced OP\u2010ASCs with biphasic calcium phosphate scaffolds significantly promoted new bone formation. These observations indicated a repression of the canonical Wnt pathway and a stimulation of the non\u2010canonical pathway in OP\u2010ASCs. Silencing <jats:italic>Wnt5a<\/jats:italic> increased the osteogenic and regenerative abilities of OP\u2010ASCs. Our study suggests targeting Wnt5a could be a promising strategy for enhancing bone regeneration in post\u2010menopausal osteoporosis.<\/jats:p>","DOI":"10.1111\/cpr.13747","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T00:15:18Z","timestamp":1726618518000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Role of Wnt5a in modulation of osteoporotic adipose\u2010derived stem cells and osteogenesis"],"prefix":"10.1111","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7819-4819","authenticated-orcid":false,"given":"Lin","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital Southwest Medical University  Luzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihong","family":"Luo","sequence":"additional","affiliation":[{"name":"Luzhou Key Laboratory of 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