Abstract

BackgroundMounting evidence indicates that circular RNAs (circRNAs) participate in the occurrence and development of various diseases, including osteoarthritis (OA). However, the effects and molecular mechanism of circ_0128846 in OA have not been reported.MethodsThe expression levels of circ_0128846, microRNA-127-5p (miR-127-5p), and nicotinamide phosphoribosyltransferase (NAMPT) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Cell viability was determined by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was examined by flow cytometry and western blot assay. Inflammatory response and cartilage extracellular matrix (ECM) degradation were evaluated by western blot assay. The relationship between miR-127-5p and circ_0128846 or NAMPT was predicted by bioinformatics tools and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays.ResultsCirc_0128846 and NAMPT were upregulated and miR-127-5p was downregulated in OA cartilage tissues. Knockdown of circ_0128846 increased cell viability and inhibited apoptosis, inflammation and ECM degradation in OA chondrocytes, while these effects were reversed by downregulating miR-127-5p. Moreover, circ_0128846 positively regulated NAMPT expression by sponging miR-127-5p. Furthermore, miR-127-5p promoted cell viability and suppressed apoptosis, inflammation, and ECM degradation in OA chondrocytes by directly targeting NAMPT.ConclusionCirc_0128846 knockdown might inhibit the progression of OA by upregulating miR-127-5p and downregulating NAMPT, offering a new insight into the potential application of circ_0128846 in OA treatment.

Highlights

  • Osteoarthritis (OA) is one of the most common joint diseases, and it is the leading cause of mobilityassociated disability [1]

  • MiR-127-5p overexpression suppressed the progression of OA by targeting nicotinamide phosphoribosyltransferase (NAMPT)

  • The results showed that the expression of circ_0128846 was greatly increased in OA cartilage tissues compared to normal cartilage tissues (Fig. 1a)

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Summary

Introduction

Osteoarthritis (OA) is one of the most common joint diseases, and it is the leading cause of mobilityassociated disability [1]. Great progress has been made, Liu et al Journal of Orthopaedic Surgery and Research (2021) 16:307 there is no effective treatment for OA [3]. OA progression is usually associated with inflammatory responses, and the major pro-inflammatory and pro-catabolic cytokines can induce matrix metalloproteinase (MMP) release [4]. More and more researchers have found that circRNAs are involved in modulation of gene expression and the development and progression of multiple diseases, including OA [7, 8]. The exact roles and regulatory mechanism of circ_0128846 in OA have not been reported. Mounting evidence indicates that circular RNAs (circRNAs) participate in the occurrence and development of various diseases, including osteoarthritis (OA). The effects and molecular mechanism of circ_0128846 in OA have not been reported

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