UBE2E3 regulates cellular senescence and osteogenic differentiation of BMSCs during aging

Yalin Liu; Guangping Cai; Peng Chen; Tiejian Jiang; Zhuying Xia

doi:10.7717/peerj.12253

UBE2E3 regulates cellular senescence and osteogenic differentiation of BMSCs during aging

PeerJ. 2021 Nov 18:9:e12253. doi: 10.7717/peerj.12253. eCollection 2021.

Authors

Yalin Liu^#¹, Guangping Cai^#¹, Peng Chen^{1

2}, Tiejian Jiang¹, Zhuying Xia¹

Affiliations

¹ Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, China.
² Department of Orthopedic, Xiangya Hospital of Central South University, Changsha, China.

^# Contributed equally.

Abstract

Background: Osteoporosis has gradually become a public health problem in the world. However, the exact molecular mechanism of osteoporosis still remains unclear. Senescence and osteogenic differentiation inhibition of bone marrow mesenchymal stem cells (BMSCs ) are supposed to play an important part in osteoporosis.

Methods: We used two gene expression profiles (GSE35956 and GSE35958) associated with osteoporosis and selected the promising gene Ubiquitin-conjugating enzyme E2 E3 (UBE2E3). We then verified its function and mechanism by in vitro experiments.

Results: UBE2E3 was highly expressed in the bone marrow and positively associated with osteogenesis related genes. Besides, UBE2E3 expression reduced in old BMSCs compared with that in young BMSCs. In in vitro experiments, knockdown of UBE2E3 accelerated cellular senescence and inhibited osteogenic differentiation of young BMSCs. On the other hand, overexpression of UBE2E3 attenuated cellular senescence as well as enhanced osteogenic differentiation of old BMSCs. Mechanistically, UBE2E3 might regulate the nuclear factor erythroid 2-related factor (Nrf2) and control its function, thus affecting the senescence and osteogenic differentiation of BMSCs.

Conclusion: UBE2E3 may be potentially involved in the pathogenesis of osteoporosis by regulating cellular senescence and osteogenic differentiation of BMSCs.

Keywords: Nrf2; Osteogenic differentiation; Osteoporosis; Senescence; UBE2E3.

Grants and funding

This work was supported by the National Natural Science Foundation of China (No: 81770877). There was no additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.