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. 2018 Oct 5;19(1):355.
doi: 10.1186/s12891-018-2273-6.

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

Jianli Xue  1 , Zixin Min  2 , Zhuqing Xia  3 , Bin Cheng  1 , Binshang Lan  1 , Fujun Zhang  2 , Yan Han  2 , Kunzheng Wang  4 , Jian Sun  2
Affiliations

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

Jianli Xue et al. BMC Musculoskelet Disord. .

Abstract

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.

Keywords: Cartilage; Osteoarthritis; SECISBP2; Selenoprotein; miRNA-181a-5p.

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Conflict of interest statement

Authors’ information

Kunzheng Wang, the corresponding author, is the Chairman of Chinese Orthopedic Association.

Ethics approval and consent to participate

This study was performed with the approval of the Ethics Committee of the Xi’an Jiaotong University Health Science Center.

All of 10 donors of OA cartilage provided full written informed consent and “Consent to publish” before the operative procedure.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Both hsa-miR-181a-5p and SBP2 are regulated by IL-1β in chondrocytes. a The expression of hsa-miRNA-181a-5p, SBP2, GPX1 and MMP13 after treatment with 10 ng/ml IL-1β for 0 (as control), 6, 12, 24 and 48 h in SW1353 cells. (n = 3, 3). b The expression of SBP2, GPX1 and MMP13 after treatment with 10 ng/ml IL-1β for 0 (as control), 6, 12, 24 and 48 h in SW1353 cells. c The expression of hsa-miRNA-181a-5p and SBP2 after treatment with 0 (as control), 1, 5, 10 and 20 ng/ml IL-1β for 12 h in SW1353 cells. (n = 3, 3). The data are expressed as the mean ± SEM; *, ** and *** indicate P < 0.05, 0.01 and 0.001, respectively
Fig. 2
Fig. 2
SBP2 regulates the biosynthesis of three selenoproteins and oxidation resistance in chondrocytes. a The expression of total (endogenous and exogenous) mSBP2 after transfection with pEGFP-N1-mSBP2 for 24 h in SW1353 cells. (n = 3, 3). b The expression of endogenous and exogenous SBP2 after transfection with pEGFP-N1-mSBP2 for 24 h in SW1353 cells. c The expression of SBP2, GPX1, GPX4 and SELS after transfection with 2 μg of pEGFP-N1-mSBP2 for 24 h in SW1353 cells. (n = 3, 3). d The expression of SBP2, GPX1, GPX4 and SELS after transfection with si-SBP2 for 24 h in SW1353 cells. (n = 3, 3). e Total GPXs activity after transfection with pEGFP-N1-mSBP2 or si-SBP2 for 24 h in SW1353 cells. (n = 3, 3). The data are expressed as the mean ± SEM; *, ** and *** indicate P < 0.05, 0.01 and 0.001, respectively
Fig. 3
Fig. 3
Transfection of miR-181a-5p affects the phenotype and oxidation resistance of chondrocytes through SBP2. a The expression of hsa-miR-181a-5p, COL2A1, ACAN and MMP13 after transfection with mimic-181a-5p for 24 h in SW1353 cells. (n = 3, 3). b The expression of hsa-miR-181a-5p, COL2A1, ACAN and MMP13 after transfection with inhibitor-181a-5p for 24 h in SW1353 cells. (n = 3, 3). c The expression of SBP2 after transfection with mimic-181a-5p or inhibitor-181a-5p for 24 h in SW1353 cells. (n = 3, 3). d The expression of SBP2 after transfection with mimic-181a-5p or inhibitor-181a-5p for 24 h in SW1353 cells. e Total GPXs activity after transfection with mimic-181a-5p or inhibitor-181a-5p for 24 h in SW1353 cells. (n = 3, 3). f The expression of mmu-miR-181a-5p, Sbp2 and SBP2 following ITS treatment in ATDC5 cells. (n = 3, 3). The data are expressed as the mean ± SEM; *, ** and *** indicate P < 0.05, 0.01 and 0.001, respectively
Fig. 4
Fig. 4
The expression of hsa-miRNA-181a-5p, SBP2 and selenoproteins in OA cartilage. a OA smooth cartilage and damaged cartilage from the same patients undergoing total knee replacement. b The expression of hsa-miRNA-181a-5p in smooth cartilage and damaged cartilage from the same OA cartilage sample. (n = 10). c The expression of SBP2 in smooth cartilage and damaged cartilage from the same OA cartilage sample. (n = 7). d The expression of SBP2 in smooth cartilage and damaged cartilage from the same OA cartilage sample. e The expression of GPX1, GPX4 and SELS in smooth cartilage and damaged cartilage from the same OA cartilage sample. (n = 8). The data were expressed as the mean ± SEM; *, ** and *** indicate P < 0.05, 0.01 and 0.001, respectively
Fig. 5
Fig. 5
The expression of hsa-miRNA-181a-5p, SBP2 and selenoproteins in peripheral blood. a The expression of hsa-miRNA-181a-5p in the peripheral blood of healthy controls and OA patients. (n = 19, 20). b The expression of SBP2 in the peripheral blood of healthy controls and OA patients. (n = 20, 20). c The expression of GPX1 in the peripheral blood of healthy controls and OA patients. (n = 20, 20). d The expression of SELS in the peripheral blood of healthy controls and OA patients. (n = 20, 19). The data are expressed as the mean ± SEM; *, ** and *** indicate P < 0.05, 0.01 and 0.001, respectively
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References

    1. Loeser RF, Collins JA, Diekman BO. Ageing and the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2016;12(7):412–420. doi: 10.1038/nrrheum.2016.65. - DOI - PMC - PubMed
    1. Mobasheri A, Rayman MP, Gualillo O, Sellam J, van der Kraan P, Fearon U. The role of metabolism in the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2017;13(5):302–311. doi: 10.1038/nrrheum.2017.50. - DOI - PubMed
    1. Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 2011;7(1):33–42. doi: 10.1038/nrrheum.2010.196. - DOI - PubMed
    1. Mitchell PG, Magna HA, Reeves LM, Lopresti-Morrow LL, Yocum SA, Rosner PJ, Geoghegan KF, Hambor JE. Cloning, expression, and type II collagenolytic activity of matrix metalloproteinase-13 from human osteoarthritic cartilage. J Clin Invest. 1996;97(3):761–768. doi: 10.1172/JCI118475. - DOI - PMC - PubMed
    1. Wang M, Sampson ER, Jin H, Li J, Ke QH, Im HJ, Chen D. MMP13 is a critical target gene during the progression of osteoarthritis. Arthritis Res Ther. 2013;15(1):R5. doi: 10.1186/ar4133. - DOI - PMC - PubMed

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