UMMS Affiliation

Shim Lab, Division of Rheumatology, Department of Medicine; Horae Gene Therapy Center; Li Weibo Institute for Rare Diseases Research

Publication Date

2021-09-24

Document Type

Article

Disciplines

Cell Biology | Developmental Biology

Abstract

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.

Keywords

FZD5, USP8, Wnt signaling, deubiquitinating enzyme, osteoblast, skeletogenesis

Rights and Permissions

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

10.3390/ijms221910289

Source

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

Journal/Book/Conference Title

International journal of molecular sciences

Related Resources

Link to Article in PubMed

PubMed ID

34638628

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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