Role of ubiquitination in the occurrence and development of osteoporosis (Review)

Int J Mol Med. 2024 Aug;54(2):68. doi: 10.3892/ijmm.2024.5392. Epub 2024 Jun 28.

Abstract

The ubiquitin (Ub)‑proteasome system (UPS) plays a pivotal role in maintaining protein homeostasis and function to modulate various cellular processes including skeletal cell differentiation and bone homeostasis. The Ub ligase E3 promotes the transfer of Ub to the target protein, especially transcription factors, to regulate the proliferation, differentiation and survival of bone cells, as well as bone formation. In turn, the deubiquitinating enzyme removes Ub from modified substrate proteins to orchestrate bone remodeling. As a result of abnormal regulation of ubiquitination, bone cell differentiation exhibits disorder and then bone homeostasis is affected, consequently leading to osteoporosis. The present review discussed the role and mechanism of UPS in bone remodeling. However, the specific mechanism of UPS in the process of bone remodeling is still not fully understood and further research is required. The study of the mechanism of action of UPS can provide new ideas and methods for the prevention and treatment of osteoporosis. In addition, the most commonly used osteoporosis drugs that target ubiquitination processes in the clinic are discussed in the current review.

Keywords: bone marrow mesenchymal cell; osteoblast; osteoclast; osteoporosis; ubiquitination.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Remodeling
  • Humans
  • Osteoporosis* / metabolism
  • Osteoporosis* / pathology
  • Proteasome Endopeptidase Complex / metabolism
  • Ubiquitin* / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination*

Substances

  • Ubiquitin
  • Proteasome Endopeptidase Complex
  • Ubiquitin-Protein Ligases

Grants and funding

The present review was supported by grants from the Qinghai Provincial Department of Science and Technology (grant no. 2022-ZJ-951Q).