E3 Ubiquitin Ligase-Mediated Regulation of Osteoblast Differentiation and Bone Formation

Jianlin Shen; Bowen Fu; Yanfang Li; Yanjiao Wu; Hongxun Sang; Heshi Zhang; Haibin Lin; Huan Liu; Wenhua Huang

doi:10.3389/fcell.2021.706395

E3 Ubiquitin Ligase-Mediated Regulation of Osteoblast Differentiation and Bone Formation

Front Cell Dev Biol. 2021 Aug 27:9:706395. doi: 10.3389/fcell.2021.706395. eCollection 2021.

Authors

Jianlin Shen^{1

2}, Bowen Fu¹, Yanfang Li³, Yanjiao Wu⁴, Hongxun Sang⁵, Heshi Zhang⁶, Haibin Lin², Huan Liu⁷, Wenhua Huang^{1

8

9}

Affiliations

¹ Guangdong Innovation Platform for Translation of 3D Printing Application, Center for Orthopaedic Surgery, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China.
² Department of Orthopedics, Affiliated Hospital of Putian University, Putian, China.
³ Department of Pediatric Surgery, Affiliated Hospital of Putian University, Putian, China.
⁴ Department of Orthopedics, Shunde Hospital of Southern Medical University, Guangzhou, China.
⁵ Department of Orthopedics, Shenzhen Hospital, Southern Medical University, Shenzhen, China.
⁶ Department of Vessel and Breast, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, China.
⁷ Department of Orthopedics, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China.
⁸ Guangdong Engineering Research Center for Translation of Medical 3D Printing Application, Guangdong Provincial Key Laboratory of Medical Biomechanics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
⁹ Orthopedic Center, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, China.

Abstract

The ubiquitin-proteasome system (UPS) is an essential pathway that regulates the homeostasis and function of intracellular proteins and is a crucial protein-degradation system in osteoblast differentiation and bone formation. Abnormal regulation of ubiquitination leads to osteoblast differentiation disorders, interfering with bone formation and ultimately leading to osteoporosis. E3 ubiquitin ligases (E3) promote addition of a ubiquitin moiety to substrate proteins, specifically recognizing the substrate and modulating tyrosine kinase receptors, signaling proteins, and transcription factors involved in the regulation of osteoblast proliferation, differentiation, survival, and bone formation. In this review, we summarize current progress in the understanding of the function and regulatory effects of E3 ligases on the transcription factors and signaling pathways that regulate osteoblast differentiation and bone formation. A deep understanding of E3 ligase-mediated regulation of osteoblast differentiation provides a scientific rationale for the discovery and development of novel E3-targeting therapeutic strategies for osteoporosis.

Keywords: E3 ubiquitin ligase; bone formation; osteoblast differentiation; signaling pathway; therapeutic target; transcription factor.

Publication types

Review