Exosomal U2AF2 derived from human bone marrow mesenchymal stem cells attenuates the intervertebral disc degeneration through circ_0036763/miR-583/ACAN axis

Xiaofeng Chen; Dongling Cai; Hao Li; Qipeng Wei; Xi Li; Zhuangxun Han; Jinjun Liang; Junxian Xie; Jiajian Ruan; Jincheng Liu; Zhen Xiang; Wenxuan Dong; Weijun Guo

doi:10.1016/j.reth.2024.01.006

Exosomal U2AF2 derived from human bone marrow mesenchymal stem cells attenuates the intervertebral disc degeneration through circ_0036763/miR-583/ACAN axis

Regen Ther. 2024 Feb 9:25:344-354. doi: 10.1016/j.reth.2024.01.006. eCollection 2024 Mar.

Authors

Xiaofeng Chen¹, Dongling Cai¹, Hao Li¹, Qipeng Wei¹, Xi Li^{2

3}, Zhuangxun Han¹, Jinjun Liang¹, Junxian Xie¹, Jiajian Ruan³, Jincheng Liu³, Zhen Xiang³, Wenxuan Dong³, Weijun Guo¹

Affiliations

¹ Department of Orthopedics, Panyu Hospital of Chinese Medicine, No.93 and 65 Qiaodong Road, Panyu District, Guangzhou 511400, China.
² Department of Dermatology, Panyu Hospital of Chinese Medicine, No.93 and 65 Qiaodong Road, Panyu District, Guangzhou 511400, China.
³ Guangzhou University of Chinese Medicine, No.12 Jichang Road, Baiyun Disitrct, Guangzhou 510405, China.

Abstract

Intervertebral disc degeneration (IDD) is one of the major leading causes of back pain affecting the patient's quality of life. However, the roles of circular RNA (circRNA) in IDD remains unclear. This study aimed to explore the function and underlying mechanism of circ_0036763 in IDD. In this study, expressions of circ_0036763, U2 small nuclear RNA auxiliary factor 2 (U2AF2), miR-583 and aggrecan (ACAN) in primary human nucleus pulposus cells (HNPCs) derived from IDD patients and healthy controls were detected by quantitative real-time reverse transcription-PCR (qRT-PCR) or Western blot (WB). The relationship between pre-circ_0036763 and U2AF2, circ_0036763 and miR-583, miR-583 and ACAN mRNA was determined by bioinformatic analysis, miRNA pull down or RNA immunoprecipitation (RIP) assay. The expressions of Collagen I and Collagen II were evaluated by WB. Co-culture of bone marrow mesenchymal stem cells (bMSCs) or bMSCs-derived exosomes and HNPCs were performed to identify the effect of U2AF2 on the mature of circ_0036763 and ACAN. Results indicated that circ_0036763, U2AF2 and ACAN were downregulated while miR-583 was upregulated in HNPCs derived from IDD patients compared with that in normal HNPCs. Besides, overexpression of circ_0036763 elevated the expressions of ACAN and Collagen II whereas reduced Collagen I expression in HNPCs. Moreover, U2AF2 promoted the mature of circ_0036763, and circ_0036763 positively regulated ACAN by directly sponging miR-583. Furthermore, exosomal U2AF2 derived from bMSCs could increase U2AF2 levels in HNPCs and subsequently regulate the expression of ACAN by circ_0036763/miR-583 axis. In summary, circ_0036763 modified by exosomal U2AF2 derived from bMSCs alleviated IDD through regulating miR-583/ACAN axis in HNPCs. Thus, this study might provide novel therapeutic targets for IDD.

Keywords: CircRNA mature; Circ_0036763; Exosomes derived from human bMSCs; Intervertebral disc degeneration; U2AF2.