{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:30:03Z","timestamp":1791304203502,"version":"4.3.1"},"reference-count":34,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,8,5]],"date-time":"2020-08-05T00:00:00Z","timestamp":1596585600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Osteogenesis imperfecta (OI), also known as \u201cbrittle bone disease,\u201d is a rare inherited genetic disorder characterized by bone fragility and often associated with short stature. The mutation in WNT1 causes autosomal recessive OI (AR\u2010OI) due to the key role of WNT\/\u03b2\u2010catenin signaling in bone formation. WNT1 mutations cause phenotypes in OI of varying degrees of clinical severity, ranging from moderate to progressively deforming forms. The nucleotide change c.677C\u00a0&gt;\u00a0T is one of the recurrent variants in the WNT1 alleles in Chinese AR\u2010OI patients. To explore the effects of mutation c.677C\u00a0&gt;\u00a0T on WNT1 function, we evaluated the activation of WNT\/\u03b2\u2010catenin signaling, cell proliferation, osteoblast differentiation, and osteoclast differentiation in WNT1<jats:sup>c.677C&gt;T<\/jats:sup>, WNT1<jats:sup>c.884C&gt;A<\/jats:sup>, and wild type WNT1 transfected into MC3T3\u2010E1 preosteoblasts. Plasmids containing wild type WNT1, WNT1<jats:sup>c.677C&gt;T<\/jats:sup>, and WNT1<jats:sup>c.884C&gt;A<\/jats:sup> cDNAs were constructed. Protein levels of phosphorylation at serine 9 of GSK\u20103\u03b2 (p\u2010GSK\u20103\u03b2), GSK\u20103\u03b2, nonphosphorylated \u03b2\u2010catenin (non\u2010p\u2010\u03b2\u2010catenin), and \u03b2\u2010catenin were detected with western blot. Cell proliferation was determined using MTS. BMP\u20102 and RANKL mRNA and protein levels were detected by qPCR and western blot. Our results showed that WNT1<jats:sup>c.677C&gt;T<\/jats:sup> failed to activate WNT\/\u03b2\u2010catenin signaling and impaired the proliferation of preosteoblasts. Moreover, compared to wild type WNT1, WNT1<jats:sup>c.677C&gt;T<\/jats:sup> downregulated BMP\u20102 protein expression and was exhibited a diminished capacity to suppress the RANKL protein level. In conclusion, mutation c.677C\u00a0&gt;\u00a0T hindered the ability of WNT1 to induce the WNT\/\u03b2\u2010catenin signaling pathway and it affected the WNT\/\u03b2\u2010catenin pathway which might potentially contribute to hampered bone homeostasis.<\/jats:p>","DOI":"10.1111\/ahg.12399","type":"journal-article","created":{"date-parts":[[2020,8,5]],"date-time":"2020-08-05T20:08:56Z","timestamp":1596658136000},"page":"447-455","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The role of WNT1 mutant variant (WNT1<sup>c.677C&gt;T<\/sup>) in osteogenesis imperfecta"],"prefix":"10.1111","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6296-281X","authenticated-orcid":false,"given":"Bashan","family":"Zhang","sequence":"first","affiliation":[{"name":"Clinical Laboratory Affiliated Dongguan People's Hospital, Southern Medical University  Dongguan 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