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Cerebro\u2010costo\u2010mandibular syndrome (CCMS) is one such spliceosomal disease, which presents as congenital skeletal dysmorphism and is caused by mutations of <jats:italic>SNRPB<\/jats:italic> gene encoding Small Nuclear Ribonucleoprotein Polypeptides B\/B\u2032 (SmB\/B\u2032). This study employed <jats:italic>in\u2009vitro<\/jats:italic> cell cultures to monitor osteo\u2010 and chondro\u2010differentiation and examined the role of SmB\/B\u2032 in the differentiation process. We found that low levels of SmB\/B\u2032 by knockdown or mutations of <jats:italic>SNRPB<\/jats:italic> led to suppressed osteodifferentiation in Saos\u20102 osteoprogenitor\u2010like cells, which was accompanied by affected splicing of <jats:italic>Dlx5<\/jats:italic>. <jats:styled-content>On the other hand, low<\/jats:styled-content> SmB\/B\u2032 led to promoted chondrogenesis in HEPM mesenchymal stem cells. Consistent with other reports, osteogenesis was promoted by the Wnt\/\u03b2\u2010catenin pathway activator and suppressed by Wnt and BMP blockers, whereas chondrogenesis was promoted by Wnt inhibitors. Suppressed osteogenic markers by <jats:italic>SNRPB<\/jats:italic> knockdown were partly rescued by Wnt\/\u03b2\u2010catenin pathway activation. Reporter analysis revealed that suppression of <jats:italic>SNRPB<\/jats:italic> results in attenuated Wnt pathway and\/or enhanced BMP pathway activities. <jats:italic>SNRPB<\/jats:italic> knockdown altered splicing of <jats:italic>TCF7L2<\/jats:italic> which impacts Wnt\/\u03b2\u2010catenin pathway activities. This work helps unravel the mechanism underlying CCMS whereby reduced expression of spliceosomal proteins causes skeletal phenotypes.<\/jats:p>","DOI":"10.1111\/febs.16934","type":"journal-article","created":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T16:21:27Z","timestamp":1692202887000},"page":"272-291","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Defects of the spliceosomal gene <i>SNRPB<\/i> affect osteo\u2010 and chondro\u2010differentiation"],"prefix":"10.1111","volume":"291","author":[{"given":"Chris","family":"Knill","sequence":"first","affiliation":[{"name":"Faculty of Life Sciences University of Bristol  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellie J.","family":"Henderson","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences University of Bristol  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