| First Author | Chaugule S | Year | 2021 |
| Journal | Int J Mol Sci | Volume | 22 |
| Issue | 19 | PubMed ID | 34638628 |
| Mgi Jnum | J:312463 | Mgi Id | MGI:6786713 |
| Doi | 10.3390/ijms221910289 | Citation | Chaugule S, et al. (2021) Deubiquitinating Enzyme USP8 Is Essential for Skeletogenesis by Regulating Wnt Signaling. Int J Mol Sci 22(19) |
| abstractText | 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. |
