Regulatory Roles of E3 Ubiquitin Ligases and Deubiquitinases in Bone
E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) are pivotal regulators of bone homeostasis, orchestrating osteoblast differentiation, proliferation, and osteoclast activity by controlling protein degradation and stability. This review delineates the roles of key E3 ligases (e.g., Smurf1, Sm...
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2025-05-01
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| Online Access: | https://www.mdpi.com/2218-273X/15/5/679 |
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| author | Haotian He Lifei Wang Bao Xian Yayi Xia |
| author_facet | Haotian He Lifei Wang Bao Xian Yayi Xia |
| author_sort | Haotian He |
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| description | E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) are pivotal regulators of bone homeostasis, orchestrating osteoblast differentiation, proliferation, and osteoclast activity by controlling protein degradation and stability. This review delineates the roles of key E3 ligases (e.g., Smurf1, Smurf2, TRIM family) and DUBs (e.g., USP family) in bone formation and resorption. E3 ligases such as Smurf1/2 inhibit osteogenesis by degrading BMP/Smad signaling components, while TRIM proteins and HERC ligases promote osteoblast differentiation. Conversely, DUBs like USP2 and USP34 stabilize β-catenin and Smad1/RUNX2, enhancing osteogenic pathways, whereas USP10 and USP12 suppress differentiation. Dysregulation of these enzymes contributes to osteoporosis, fracture non-union, and other bone disorders. The interplay between ubiquitination and deubiquitination, alongside the regulatory role of miRNA and environmental factors, underscores their therapeutic potential. Future research should focus on developing therapies targeting E3 ubiquitin ligases, deubiquitinases, miRNA regulators, and small-molecule inhibitors to restore bone homeostasis in osteoporosis and fracture healing disorders. |
| format | Article |
| id | doaj-art-ba7fa5174b644982bff4891c93b703e2 |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Biomolecules |
| spelling | doaj-art-ba7fa5174b644982bff4891c93b703e22025-08-20T03:47:53ZengMDPI AGBiomolecules2218-273X2025-05-0115567910.3390/biom15050679Regulatory Roles of E3 Ubiquitin Ligases and Deubiquitinases in BoneHaotian He0Lifei Wang1Bao Xian2Yayi Xia3Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou 730030, ChinaDepartment of Orthopedics, Lanzhou University Second Hospital, Lanzhou 730030, ChinaDepartment of Orthopedics, Lanzhou University Second Hospital, Lanzhou 730030, ChinaDepartment of Orthopedics, Lanzhou University Second Hospital, Lanzhou 730030, ChinaE3 ubiquitin ligases and deubiquitinating enzymes (DUBs) are pivotal regulators of bone homeostasis, orchestrating osteoblast differentiation, proliferation, and osteoclast activity by controlling protein degradation and stability. This review delineates the roles of key E3 ligases (e.g., Smurf1, Smurf2, TRIM family) and DUBs (e.g., USP family) in bone formation and resorption. E3 ligases such as Smurf1/2 inhibit osteogenesis by degrading BMP/Smad signaling components, while TRIM proteins and HERC ligases promote osteoblast differentiation. Conversely, DUBs like USP2 and USP34 stabilize β-catenin and Smad1/RUNX2, enhancing osteogenic pathways, whereas USP10 and USP12 suppress differentiation. Dysregulation of these enzymes contributes to osteoporosis, fracture non-union, and other bone disorders. The interplay between ubiquitination and deubiquitination, alongside the regulatory role of miRNA and environmental factors, underscores their therapeutic potential. Future research should focus on developing therapies targeting E3 ubiquitin ligases, deubiquitinases, miRNA regulators, and small-molecule inhibitors to restore bone homeostasis in osteoporosis and fracture healing disorders.https://www.mdpi.com/2218-273X/15/5/679bone homeostasisE3 ubiquitin ligasesDUBsosteoblast differentiationubiquitination |
| spellingShingle | Haotian He Lifei Wang Bao Xian Yayi Xia Regulatory Roles of E3 Ubiquitin Ligases and Deubiquitinases in Bone Biomolecules bone homeostasis E3 ubiquitin ligases DUBs osteoblast differentiation ubiquitination |
| title | Regulatory Roles of E3 Ubiquitin Ligases and Deubiquitinases in Bone |
| title_full | Regulatory Roles of E3 Ubiquitin Ligases and Deubiquitinases in Bone |
| title_fullStr | Regulatory Roles of E3 Ubiquitin Ligases and Deubiquitinases in Bone |
| title_full_unstemmed | Regulatory Roles of E3 Ubiquitin Ligases and Deubiquitinases in Bone |
| title_short | Regulatory Roles of E3 Ubiquitin Ligases and Deubiquitinases in Bone |
| title_sort | regulatory roles of e3 ubiquitin ligases and deubiquitinases in bone |
| topic | bone homeostasis E3 ubiquitin ligases DUBs osteoblast differentiation ubiquitination |
| url | https://www.mdpi.com/2218-273X/15/5/679 |
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