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

Autor: Binshang Lan, Zhuqing Xia, Jian Sun, Jianli Xue, Bin Cheng, Kunzheng Wang, Fujun Zhang, Zixin Min, Yan Han
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Cartilage
Articular
Male
0301 basic medicine
GPX1
lcsh:Diseases of the musculoskeletal system
Cellular differentiation
Interleukin-1beta
Down-Regulation
Osteoarthritis
Selenoprotein
Chondrocyte
03 medical and health sciences
Chondrocytes
Glutathione Peroxidase GPX1
Rheumatology
Cell Line
Tumor
medicine
Humans
Orthopedics and Sports Medicine
RNA
Messenger
RNA
Small Interfering
Aged
miRNA-181a-5p
Glutathione Peroxidase
Selenocysteine insertion sequence binding
Cartilage homeostasis
business.industry
Cartilage
RNA-Binding Proteins
Cell Differentiation
Middle Aged
Phospholipid Hydroperoxide Glutathione Peroxidase
medicine.disease
Extracellular Matrix
Up-Regulation
Metabolism disorder
Cell biology
MicroRNAs
Oxidative Stress
030104 developmental biology
medicine.anatomical_structure
SECISBP2
Female
lcsh:RC925-935
business
Research Article
Signal Transduction
Zdroj: BMC Musculoskeletal Disorders, Vol 19, Iss 1, Pp 1-10 (2018)
BMC Musculoskeletal Disorders
ISSN: 1471-2474
DOI: 10.1186/s12891-018-2273-6
Popis: Background 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. 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. Methods To 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. Results The 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. Conclusion Overall, 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 material The online version of this article (10.1186/s12891-018-2273-6) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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