CircMYO1C silencing alleviates chondrocytes inflammation and apoptosis through m6A/HMGB1 axis in osteoarthritis

Haitao Sun; Xudong Chu; Weiqing Qian; Hong Yin

doi:10.1002/bab.2635

CircMYO1C silencing alleviates chondrocytes inflammation and apoptosis through m⁶A/HMGB1 axis in osteoarthritis

Biotechnol Appl Biochem. 2024 Jul 9. doi: 10.1002/bab.2635. Online ahead of print.

Authors

Haitao Sun¹, Xudong Chu¹, Weiqing Qian², Hong Yin²

Affiliations

¹ Department of Orthopedic Surgery, Wuxi Huishan District People's Hospital, Affiliated Huishan Hospital of Xinglin College, Nantong University, Wuxi, Jiangsu, China.
² Department of Orthopedic, Third Affiliated Hospital, Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu, China.

PMID: 38982736
DOI: 10.1002/bab.2635

Abstract

Circular RNAs (circRNAs) are involved in osteoarthritis (OA) progression. This study aimed to investigate the role and molecular mechanisms of circMYO1C in OA. CircMYO1C was upregulated in OA- and interleukin-1β (IL-1β)-exposed chondrocytes. The results indicated that circMYO1C knockdown repressed the inflammatory factors (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], interleukin-8 [IL-8], etc.) and apoptosis of chondrocytes following IL-1β exposure. CircMYO1C was an N⁶-methyladenosine (m⁶A)-modified circRNA with m6A characteristics. High mobility group box 1 (HMGB1) was a target of circMYO1C. IL-1β exposure increased the stability and half-life (t_1/2) of HMGB1 mRNA, while silencing circMYO1C reduced HMGB1 mRNA stability. Taken together, circMYO1C targets the m6A/HMGB1 axis to promote chondrocyte apoptosis and inflammation. The present study demonstrates that the circMYO1C/m6A/HMGB1 axis is essential for OA progression, highlighting a novel potential therapeutic target for clinical OA.

Keywords: HMGB1 osteoarthritis; circMYO1C; circular RNAs.