Abstract
Circular RNA derived from vacuolar ATPase assembly factor (VMA21) has been proven to be an inflammation suppressor in many diseases, while its role in osteoarthritis (OA) is unknown. We predicted that VMA21 participates in OA via interacting with miR-103, an OA promoter. Therefore, we analyzed the crosstalk between VMA21 and miR-103 in OA. In this study, the levels of VMA21, pre-miR-103, and mature miR-103 in synovial fluid samples from OA patients (n = 56) and controls (n = 56) were analyzed using RT-qPCR. Nuclear and cytoplasm samples were prepared from chondrocytes, and VMA21 expression was detected by RT-PCR. RNA–RNA pulldown assay was applied to analyze the direct interaction between VMA21 and pre-miR-103. The involvement of VMA21 and miR-103 in lipopolysaccharide (LPS)-induced chondrocyte apoptosis and viability was analyzed using cell apoptosis assay and 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, respectively. We found that compared to the control group, VMA21 expression was decreased in OA, and miR-103 maturation was increased in OA. VMA21 could be detected in both nuclear and cytoplasm, and VMA21 directly interacted with pre-miR-103. VMA21 overexpression reduced miR-103 maturation. VMA21 suppressed the role of miR-103 in enhancing chondrocyte apoptosis and reducing cell viability after LPS treatment. In conclusion, VMA21 might suppress LPS-induced chondrocyte apoptosis in OA by decreasing the production of mature miR-103.
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The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to their containing information that could compromise the privacy of research participants.
References
Krishnan, Y., & Grodzinsky, A. J. (2018). Cartilage diseases. Matrix Biology: Journal of the International Society for Matrix Biology, 71–72, 51–69. https://doi.org/10.1016/j.matbio.2018.05.005
Hawker, G. A. (2019). Osteoarthritis is a serious disease. Clinical and Experimental Rheumatology, 37(Suppl 120), 3–6.
Kloppenburg, M., & Berenbaum, F. (2020). Osteoarthritis year in review 2019: Epidemiology and therapy. Osteoarthritis and Cartilage, 28(3), 242–248. https://doi.org/10.1016/j.joca.2020.01.002
Rahmati, M., Nalesso, G., Mobasheri, A., & Mozafari, M. (2017). Aging and osteoarthritis: Central role of the extracellular matrix. Ageing Research Reviews, 40, 20–30. https://doi.org/10.1016/j.arr.2017.07.004
Collins, J. A., Diekman, B. O., & Loeser, R. F. (2018). Targeting aging for disease modification in osteoarthritis. Current Opinion in Rheumatology, 30(1), 101–107. https://doi.org/10.1097/bor.0000000000000456
O’Connell, N. E., Smith, K. J., Peterson, M. D., Ryan, N., Liverani, S., Anokye, N., Victor, C., & Ryan, J. M. (2019). Incidence of osteoarthritis, osteoporosis and inflammatory musculoskeletal diseases in adults with cerebral palsy: A population-based cohort study. Bone, 125, 30–35. https://doi.org/10.1016/j.bone.2019.05.007
Callahan, L. F., Ambrose, K. R., Albright, A. L., Altpeter, M., Golightly, Y. M., Huffman, K. F., Nelson, A. E., & Weisner, S. E. (2019). Public Health Interventions for Osteoarthritis—Updates on the Osteoarthritis Action Alliance’s efforts to address the 2010 OA Public Health Agenda Recommendations. Clinical and Experimental Rheumatology, 37(Suppl 120), 31–39.
Gu, Y. T., Chen, J., Meng, Z. L., Ge, W. Y., Bian, Y. Y., Cheng, S. W., Xing, C. K., Yao, J. L., Fu, J., & Peng, L. (2017). Research progress on osteoarthritis treatment mechanisms. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 93, 1246–1252. https://doi.org/10.1016/j.biopha.2017.07.034
Roseti, L., Desando, G., Cavallo, C., Petretta, M., & Grigolo, B. (2019). Articular cartilage regeneration in osteoarthritis. Cells. https://doi.org/10.3390/cells8111305
Grässel, S., & Aszodi, A. (2019). Osteoarthritis and cartilage regeneration: Focus on pathophysiology and molecular mechanisms. International Journal of Molecular Science. https://doi.org/10.3390/ijms20246156
Zhang, M., Theleman, J. L., Lygrisse, K. A., & Wang, J. (2019). Epigenetic mechanisms underlying the aging of articular cartilage and osteoarthritis. Gerontology, 65(4), 387–396. https://doi.org/10.1159/000496688
Verduci, L., Tarcitano, E., Strano, S., Yarden, Y., & Blandino, G. (2021). CircRNAs: Role in human diseases and potential use as biomarkers. Cell Death & Disease, 12(5), 468. https://doi.org/10.1038/s41419-021-03743-3
Liu, Q., Zhang, X., Hu, X., Yuan, L., Cheng, J., Jiang, Y., & Ao, Y. (2017). Emerging roles of circRNA related to the mechanical stress in human cartilage degradation of osteoarthritis. Molecular Therapy Nucleic Acids, 7, 223–230. https://doi.org/10.1016/j.omtn.2017.04.004
Shi, Y., Sun, C. F., Ge, W. H., Du, Y. P., & Hu, N. B. (2020). Circular RNA VMA21 ameliorates sepsis-associated acute kidney injury by regulating miR-9-3p/SMG1/inflammation axis and oxidative stress. Journal of Cellular and Molecular Medicine, 24(19), 11397–11408. https://doi.org/10.1111/jcmm.15741
Li, F., Yao, J., Hao, Q., & Duan, Z. (2019). miRNA-103 promotes chondrocyte apoptosis by down-regulation of Sphingosine kinase-1 and ameliorates PI3K/AKT pathway in osteoarthritis. Bioscience Reports. https://doi.org/10.1042/bsr20191255
Yang, P., Gao, R., Zhou, W., & Han, A. (2020). Protective impacts of circular RNA VMA21 on lipopolysaccharide-engendered WI-38 cells injury via mediating microRNA-142-3p. BioFactors (Oxford, England), 46(3), 381–390. https://doi.org/10.1002/biof.1593
Huang, Z. Y., Stabler, T., Pei, F. X., & Kraus, V. B. (2016). Both systemic and local lipopolysaccharide (LPS) burden are associated with knee OA severity and inflammation. Osteoarthritis and Cartilage, 24(10), 1769–1775. https://doi.org/10.1016/j.joca.2016.05.008
Hwang, H. S., & Kim, H. A. (2015). Chondrocyte apoptosis in the pathogenesis of osteoarthritis. International journal of molecular sciences, 16(11), 26035–26054. https://doi.org/10.3390/ijms161125943
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DY: study concepts, literature research, clinical studies, data analysis, experimental studies, manuscript writing, and review; DY, XH: study design, literature research, experimental studies, and manuscript editing; YC: definition of intellectual content, clinical studies, data acquisition, and statistical analysis; CW: data acquisition, manuscript preparation, and data analysis. All authors have read and approve the submission of the manuscript.
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Yang, D., Hu, X., Chen, Y. et al. Circular RNA Derived from Vacuolar ATPase Assembly Factor VMA21 Suppresses Lipopolysaccharide-Induced Apoptosis of Chondrocytes in Osteoarthritis (OA) by Decreasing Mature miR-103 Production. Mol Biotechnol 64, 825–831 (2022). https://doi.org/10.1007/s12033-022-00451-x
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DOI: https://doi.org/10.1007/s12033-022-00451-x