Knockdown of Circ_SLC39A8 protects against the progression of osteoarthritis by regulating miR-591/IRAK3 axis

Jizhe Yu,Naxin Zhou,Yushuang Qin

doi:10.1186/s13018-021-02323-7

Abstract

BackgroundThe dysregulation of circular RNAs (circRNAs) has been identified in various human diseases, including osteoarthritis (OA). The purpose of this study was to identify the role and mechanism of circ_SLC39A8 in regulating the progression of OA.MethodsThe expression levels of circ_SLC39A8, miR-591, and its potential target gene, interleukin-1-receptor-associated kinase 3 (IRAK3), were identified by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. The relationship between miR-591 and circ_SLC39A8 or IRAK3 was predicted by bioinformatics tools and verified by dual-luciferase reporter.ResultsCirc_SLC39A8 and IRAK3 were upregulated and miR-591 was downregulated in OA cartilage tissues. Knockdown of circ_SLC39A8 inhibited apoptosis and inflammation in OA chondrocytes, while these effects were reversed by downregulating miR-591. Promotion cell viability effects of miR-591 were partially reversed by IRAK3 overexpression.ConclusionOur findings indicated that knockdown of circ_SLC39A8 delayed the progression of OA via modulating the miR-591-IRAK3 axis, providing new insight into the molecular mechanisms of OA pathogenesis.

Highlights

Osteoarthritis (OA) is the most common joint disease and is recognized as one of the leading causes of pain and disability among the elderly [1, 2]
Knockdown of circ_SLC39A8 increased cell viability and inhibited apoptosis, inflammation, and Extracellular matrix (ECM) degradation in OA chondrocytes To explore the effect of circ_SLC39A8 on OA progression, knockdown of circ_SLC39A8 was constructed and the knockdown efficiency was determined by quantitative real-time polymerase chain reaction (qRT-PCR)
The results indicated that the luciferase activity of interleukin-1-receptorassociated kinase 3 (IRAK3)-wt was markedly reduced post-transfection with miR-591 mimic (miR-591); no change was observed in the activity of cells transfected with IRAK3-mut in the presence of miR-591 (Fig. 5a)

Summary

Introduction

Osteoarthritis (OA) is the most common joint disease and is recognized as one of the leading causes of pain and disability among the elderly [1, 2]. OA is primarily characterized by degradation of the articular cartilage, as well as subchondral bone sclerosis, and osteophyte formation. OA is a global health problem and the most common joint disorder disease [3, 4]. The manifestations of OA cartilage are mainly accumulation of senescent cells, cell loss, and extracellular matrix destruction. Patients with OA have higher levels of inflammatory biomarkers. Inflammatory cytokines interfere with the catabolism of bones and joints, causing severe pain and even disability [9]. The dysregulation of circular RNAs (circRNAs) has been identified in various human diseases, including osteoarthritis (OA). The purpose of this study was to identify the role and mechanism of circ_SLC39A8 in regulating the progression of OA

Objectives

Methods

Results

Discussion

Conclusion