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

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.Electronic supplementary materialThe online version of this article (10.1186/s12891-018-2273-6) contains supplementary material, which is available to authorized users.

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“…Furthermore, GPX family members are targeted by miRNAs and results in defect of ROS neutralization. In one report, GPX4 was decreased by miR-181a-5p in osteoarthritis 55 . However, the relationship between GPX4 and miRNAs in cancer is still in dark.…”

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“…At the same time, GPX1 and GPX4 are upgraded. A decreased expression of GPX1 and GPX4 mRNA and expression of SBP2 protein are detected in damaged cartilage but not in smooth cartilage from the same osteoarthritis sample, and vice versa, decreased expression of hsa-miR-181a-5p is also noted (Xue et al, 2018).…”

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“…Various previous studies have shown that the abnormal expressions of miRNAs are closely related to the development of OA [14,15]. As reported, after the occurrence of OA, miR-181a-5p is abnormally downregulated and the in-depth mechanism research nds that miR-181a-5p plays an important role in the process of OA by negatively regulating SBP2 [16]. Besides, Chen et al found that miR-29b-3p promotes chondrocyte apoptosis and promotes the occurrence and development of OA through targeting PGRN [17].…”