The hsa-miR-181a-5p reduces oxidation resistance by controlling SECISBP2 in osteoarthritis

Jianli Xue,Kunzheng Wang,Bin Cheng,Zhuqing Xia,Binshang Lan,Fujun Zhang,Yan Han,Jian Sun,Zixin Min

doi:10.1186/s12891-018-2273-6

Abstract

BackgroundThe phenotypes of osteoarthritis (OA) consist of cartilage extracellular matrix (ECM) metabolism disorder and the breakdown of cartilage homeostasis, which are induced by pro-inflammatory factors and oxidative stress. Selenoproteins regulated by selenocysteine insertion sequence binding protein 2 (SBP2) are highly effective antioxidants, but their regulatory mechanisms, particularly the involvement of miRNAs, are not fully understood.MethodsTo explore whether miR-181a-5p and SBP2 are involved in OA pathogenesis, we established an IL-1β model using the chondrocyte SW1353 cell line. Next, we up- or down-regulated SBP2 and miRNA-181a-5p expression in the cells. Finally, we measured the expression of miRNA-181a-5p, SBP2 and three selenoproteins in OA cartilage and peripheral blood.ResultsThe results showed that IL-1β increased hsa-miR-181a-5p and decreased SBP2 in a time- and dose-dependent manner. GPX1 and GPX4, which encode crucial glutathione peroxidase antioxidant enzymes, were up-regulated along with SBP2 and miR-181a-5p. Furthermore, SBP2 showed a significant negative correlation with miR-181a-5p during induced ATDC5 cell differentiation. There was lower GPX1 and GPX4 mRNA expression and SBP2 protein expression in damaged cartilage than in smooth cartilage from the same OA sample, and hsa-miR-181a-5p expression on the contrary. Similar results were observed in peripheral blood. In conclusion, we have reported a novel pathway in which pro-inflammatory factors, miRNA, SBP2 and selenoproteins are associated with oxidation resistance in cartilage.ConclusionOverall, this study provides the first comprehensive evidence that pro-inflammatory factors cause changes in the cartilage antioxidant network and describes the discovery of novel mediators of cartilage oxidative stress and OA pathophysiology. Our data suggest that miR-181a-5p may be used to develop novel early-stage diagnostic and therapeutic strategies for OA.

Highlights

The phenotypes of osteoarthritis (OA) consist of cartilage extracellular matrix (ECM) metabolism disorder and the breakdown of cartilage homeostasis, which are induced by pro-inflammatory factors and oxidative stress
Using GraphPad Prism 6.0 (GraphPad Software, San Diego, CA, USA). Both hsa-miR-181a-5p and sequence binding protein 2 (SBP2) are regulated by Including interleukin-1 (IL-1β) in chondrocytes IL-1β was selected to stimulate SW1353 cells, and hsamiR-181a-5p expression levels were determined by stem loop RT-qPCR
SBP2 regulated the biosynthesis of three selenoproteins and oxidation resistance in chondrocytes To assess the role of SBP2 in chondrocytes, we constructed recombinant hSBP2-CDS clones and si-SBP2 (Fig. 2a) and transfected these constructs into SW1353 cells

Summary

Introduction

The phenotypes of osteoarthritis (OA) consist of cartilage extracellular matrix (ECM) metabolism disorder and the breakdown of cartilage homeostasis, which are induced by pro-inflammatory factors and oxidative stress. The phenotypes of cartilage injury processes induced by pro-inflammatory factors are Reactive oxygen species (ROS) are products of aerobic metabolism that injure DNA, proteins, and cellular membranes [9,10,11]. Selenoproteins (Sel) are important members of a network of antioxidant enzymatic systems and minimize damage induced by ROS. They contain selenocysteine (Sec), the 21st proteinogenic amino acid, which is named after the essential biological trace element selenium (Se) and acts as an active-site residue essential for the catalytic activity of selenoproteins [9,10,11]. The function of SBP2 is to carry Sec-tRNASec into the ribosome ‘A site’ to recognize ‘UGA’ as the Sec codon during selenoprotein synthesis [15, 16]

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Discussion

Conclusion