The miR-548d-5p/SP1 signaling axis regulates chondrocyte proliferation and inflammatory responses in osteoarthritis

Yusheng Li; Wenqing Xie; Yizi Zheng; Hengzhen Li; Zeqin Wen; Chen Wang; Siyu Chen; Zhenhan Deng

doi:10.1016/j.intimp.2022.109029

The miR-548d-5p/SP1 signaling axis regulates chondrocyte proliferation and inflammatory responses in osteoarthritis

Int Immunopharmacol. 2022 Sep:110:109029. doi: 10.1016/j.intimp.2022.109029. Epub 2022 Jul 20.

Authors

Yusheng Li¹, Wenqing Xie², Yizi Zheng³, Hengzhen Li², Zeqin Wen⁴, Chen Wang⁵, Siyu Chen⁵, Zhenhan Deng⁶

Affiliations

¹ Department of Orthopedics, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
² Department of Orthopedics, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.
³ Department of Thyroid and Breast Surgery, Shenzhen Breast Tumor Research Center for Diagnosis and Treatment, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, Guangdong, China.
⁴ Department of Clinical Medicine, Xiangya School of Medicine of Central South University, Changsha 518035, Hunan, China.
⁵ Department of Sports Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, Guangdong, China.
⁶ Department of Sports Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen 518035, Guangdong, China. Electronic address: dengzhenhan@email.szu.edu.cn.

PMID: 35978504
DOI: 10.1016/j.intimp.2022.109029

Abstract

Chondrocyte apoptosis and dysfunction play an important role in osteoarthritis (OA), a chronic progressive arthropathy. Non-coding RNAs have been implicated in OA pathogenesis. In this study, microRNA (miR)-548d-5p was found to be downregulated in OA samples and IL-1β-stimulated chondrocytes. miR-548d-5p overexpression partially reversed IL-1β-induced chondrocyte damage in vitro, evidenced by the promotion of cell growth, the inhibition of apoptosis and inflammatory cytokine release, and the improvement in extracellular matrix (ECM) deposition. Furthermore, miR-548d-5p overexpression partially reversed papain-induced damages on OA rat's knee articular cartilage. Specificity protein 1 (SP1) was inhibited by miR-548d-5p and identified as its direct downstream target. In IL-1β-stimulated chondrocytes, SP1 overexpression significantly attenuated the protective effects of miR-548d-5p overexpression against chondrocyte damage. In conclusion, miR-548d-5p was abnormally downregulated in OA samples and IL-1β-stimulated chondrocytes. miR-548d-5p protects against IL-1β-induced chondrocyte damage via direct inhibition of SP1.

Keywords: Chondrocyte; MicroRNA-548d-5p; Osteoarthritis; Specificity protein 1.

MeSH terms

Animals
Apoptosis
Cell Proliferation
Chondrocytes
Interleukin-1beta / metabolism
MicroRNAs* / genetics
MicroRNAs* / metabolism
Osteoarthritis* / metabolism
Rats

Substances

Interleukin-1beta
MicroRNAs