Shim Lab, Division of Rheumatology, Department of Medicine; Horae Gene Therapy Center; Li Weibo Institute for Rare Diseases Research
Cell Biology | Developmental Biology
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.
FZD5, USP8, Wnt signaling, deubiquitinating enzyme, osteoblast, skeletogenesis
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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/).
DOI of Published Version
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. Link to article on publisher's site
International journal of molecular sciences
Chaugule S, Kim J, Yang Y, Knobeloch K, He X, Shim J. (2021). Deubiquitinating Enzyme USP8 Is Essential for Skeletogenesis by Regulating Wnt Signaling. Open Access Publications by UMass Chan Authors. https://doi.org/10.3390/ijms221910289. Retrieved from https://escholarship.umassmed.edu/oapubs/4949
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This work is licensed under a Creative Commons Attribution 4.0 License.