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dc.contributor.authorChaugule, Sachin
dc.contributor.authorKim, Jung-Min
dc.contributor.authorYang, Yeon-Suk
dc.contributor.authorKnobeloch, Klaus-Peter
dc.contributor.authorHe, Xi
dc.contributor.authorShim, Jae-Hyuck
dc.date2022-08-11T08:10:06.000
dc.date.accessioned2022-08-23T16:55:23Z
dc.date.available2022-08-23T16:55:23Z
dc.date.issued2021-09-24
dc.date.submitted2022-06-02
dc.identifier.citation<p>Chaugule S, Kim JM, Yang YS, Knobeloch KP, He X, Shim JH. Deubiquitinating Enzyme USP8 Is Essential for Skeletogenesis by Regulating Wnt Signaling. Int J Mol Sci. 2021 Sep 24;22(19):10289. doi: 10.3390/ijms221910289. PMID: 34638628; PMCID: PMC8508692. <a href="https://doi.org/10.3390/ijms221910289">Link to article on publisher's site</a></p>
dc.identifier.issn1422-0067 (Linking)
dc.identifier.doi10.3390/ijms221910289
dc.identifier.pmid34638628
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42705
dc.description.abstractDisturbance in a differentiation program of skeletal stem cells leads to indecorous skeletogenesis. Growing evidence suggests that a fine-tuning of ubiquitin-mediated protein degradation is crucial for skeletal stem cells to maintain their stemness and osteogenic potential. Here, we demonstrate that the deubiquitinating enzyme (DUB) ubiquitin-specific protease 8 (USP8) stabilizes the Wnt receptor frizzled 5 (FZD5) by preventing its lysosomal degradation. This pathway is essential for Wnt/beta-catenin signaling and the differentiation of osteoprogenitors to mature osteoblasts. Accordingly, deletion of USP8 in osteoprogenitors (Usp8(Osx)) resulted in a near-complete blockade in skeletal mineralization, similar to that seen in mice with defective Wnt/beta-catenin signaling. Likewise, transplanting USP8-deficient osteoprogenitors under the renal capsule in wild-type secondary hosts did not to induce bone formation. Collectively, this study unveils an essential role for the DUB USP8 in Wnt/beta-catenin signaling in osteoprogenitors and osteogenesis during skeletal development.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=34638628&dopt=Abstract">Link to Article in PubMed</a></p>
dc.rightsCopyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectFZD5
dc.subjectUSP8
dc.subjectWnt signaling
dc.subjectdeubiquitinating enzyme
dc.subjectosteoblast
dc.subjectskeletogenesis
dc.subjectCell Biology
dc.subjectDevelopmental Biology
dc.titleDeubiquitinating Enzyme USP8 Is Essential for Skeletogenesis by Regulating Wnt Signaling
dc.typeJournal Article
dc.source.journaltitleInternational journal of molecular sciences
dc.source.volume22
dc.source.issue19
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=5984&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/4949
dc.identifier.contextkey29511281
refterms.dateFOA2022-08-23T16:55:24Z
html.description.abstract<p>Disturbance in a differentiation program of skeletal stem cells leads to indecorous skeletogenesis. Growing evidence suggests that a fine-tuning of ubiquitin-mediated protein degradation is crucial for skeletal stem cells to maintain their stemness and osteogenic potential. Here, we demonstrate that the deubiquitinating enzyme (DUB) ubiquitin-specific protease 8 (USP8) stabilizes the Wnt receptor frizzled 5 (FZD5) by preventing its lysosomal degradation. This pathway is essential for Wnt/beta-catenin signaling and the differentiation of osteoprogenitors to mature osteoblasts. Accordingly, deletion of USP8 in osteoprogenitors (Usp8(Osx)) resulted in a near-complete blockade in skeletal mineralization, similar to that seen in mice with defective Wnt/beta-catenin signaling. Likewise, transplanting USP8-deficient osteoprogenitors under the renal capsule in wild-type secondary hosts did not to induce bone formation. Collectively, this study unveils an essential role for the DUB USP8 in Wnt/beta-catenin signaling in osteoprogenitors and osteogenesis during skeletal development.</p>
dc.identifier.submissionpathoapubs/4949
dc.contributor.departmentLi Weibo Institute for Rare Diseases Research
dc.contributor.departmentHorae Gene Therapy Center
dc.contributor.departmentShim Lab, Division of Rheumatology, Department of Medicine
dc.source.pages10289


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Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Except where otherwise noted, this item's license is described as Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).