E3 ubiquitin ligases: key regulators of osteogenesis and potential therapeutic targets for bone disorders

Front Cell Dev Biol. 2024 Aug 15:12:1447093. doi: 10.3389/fcell.2024.1447093. eCollection 2024.

Abstract

Ubiquitination is a crucial post-translational modification of proteins that mediates the degradation or functional regulation of specific proteins. This process participates in various biological processes such as cell growth, development, and signal transduction. E3 ubiquitin ligases play both positive and negative regulatory roles in osteogenesis and differentiation by ubiquitination-mediated degradation or stabilization of transcription factors, signaling molecules, and cytoskeletal proteins. These activities affect the proliferation, differentiation, survival, and bone formation of osteoblasts (OBs). In recent years, advances in genomics, transcriptomics, and proteomics have led to a deeper understanding of the classification, function, and mechanisms of action of E3 ubiquitin ligases. This understanding provides new insights and approaches for revealing the molecular regulatory mechanisms of bone formation and identifying therapeutic targets for bone metabolic diseases. This review discusses the research progress and significance of the positive and negative regulatory roles and mechanisms of E3 ubiquitin ligases in the process of osteogenic differentiation. Additionally, the review highlights the role of E3 ubiquitin ligases in bone-related diseases. A thorough understanding of the role and mechanisms of E3 ubiquitin ligases in osteogenic differentiation could provide promising therapeutic targets for bone tissue engineering based on stem cells.

Keywords: E3 ubiquitin ligases; bone-related diseases; osteoblast differentiation; osteogenesis; therapeutic targets.

Publication types

  • Review

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Natural Science Foundation of China (82160417); Doctoral Research Fund Project of the First Affiliated Hospital of Kunming Medical University (2022BS013); Yunnan Province Department of Science and Technology-Kunming Medical University Joint Special Project (202101AY070001-013; 202201AY070001-057); Major Science and Technology Project of Yunnan Provincial Department of Science and Technology, Yunnan Provincial Orthopedic and Sports Rehabilitation Clinical Medicine Research Center (202102AA310068); Yunnan Provincial Department of Science and Technology Basic Research Program Youth Project (202401AU070046); Yunnan Provincial Department of Education Scientific Research Fund Teacher Category Project-Young Talent Basic Research Special Fund (2024J0180). Clinical Medical Technology Innovation Guidance Project of Hunan Province (2021SK51717). Major Science and Technology Project of Yunnan Provincial Department of Science and Technology (202402AD080006).