Login Register Cart 0
Generic placeholder image

Current Molecular Medicine

Editor-in-Chief

ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

MicroRNAs in the Pathogenesis of Ankylosing Spondylitis and their Clinical Implication

Author(s): Lanqing Fu*, Guobo Wang, Wei Deng and Yu Lu*

Volume 23, Issue 10, 2023

Published on: 16 November, 2022

Page: [1058 - 1065] Pages: 8

DOI: 10.2174/1566524023666221103155119

Price: $65

Abstract

Ankylosing spondylitis (AS) is a chronic and progressive immunoinflammatory disease, which mainly affects the spine and sacroiliac joints and shows a high rate of late disability. Inflammation, bone destruction, and new bone formation are typical pathological changes of AS. AS is dominated by inflammation at the early stage. While bone destruction and heterotopic ossification, the two contradictory manifestations of AS, occur at a later stage and reflect the imbalance between osteogenesis and osteoclastogenesis in AS patients. Till now, the pathogenesis of AS remains unclear. MicroRNAs (miRNAs) are a class of highly conserved single-stranded noncoding RNAs (ncRNAs) with a length of about 22 bases characterized by temporal sequence and tissue specificity. MiRNAs are key modulators in bone formation, resorption, remodeling and regeneration by regulating the immune responses and the differentiation and functions of osteoblasts, osteoclasts and chondrocytes. The present review summarizes the roles and potential mechanisms of miRNAs’ involvement in AS by regulating immuno-inflammatory responses, bone destruction, heterotopic ossification, cell death and autophagy, and the involved signaling including the Wnt/β-catenin and BMP/Smads pathways. In addition, the feasibility of miRNAs as diagnostic biomarkers and therapeutic targets for AS are also discussed.

« Previous Next »
[1]
Golder V, Schachna L. Ankylosing spondylitis: An update. Aust Fam Physician 2013; 42(11): 780-4.
[PMID: 24217097]
[2]
Motta F, Pederzani A, Carena MC, et al. MicroRNAs in axial spondylarthritis: An overview of the recent progresses in the field with a focus on ankylosing spondylitis and psoriatic arthritis. Curr Rheumatol Rep 2021; 23(8): 59.
[http://dx.doi.org/10.1007/s11926-021-01027-5] [PMID: 34216293]
[3]
Baum R, Gravallese EM. Bone as a target organ in rheumatic disease: Impact on osteoclasts and osteoblasts. Clin Rev Allergy Immunol 2016; 51(1): 1-15.
[http://dx.doi.org/10.1007/s12016-015-8515-6] [PMID: 26411424]
[4]
Westerveld LA, Verlaan JJ, Oner FC. Spinal fractures in patients with ankylosing spinal disorders: A systematic review of the literature on treatment, neurological status and complications. Eur Spine J 2009; 18(2): 145-56.
[http://dx.doi.org/10.1007/s00586-008-0764-0] [PMID: 18791749]
[5]
Reveille JD, Weisman MH. The epidemiology of back pain, axial spondyloarthritis and HLA-B27 in the United States. Am J Med Sci 2013; 345(6): 431-6.
[http://dx.doi.org/10.1097/MAJ.0b013e318294457f] [PMID: 23841117]
[6]
Simone D, Al Mossawi MH, Bowness P. Progress in our understanding of the pathogenesis of ankylosing spondylitis. Rheumatology 2018; 57(S6): vi4-9.
[http://dx.doi.org/10.1093/rheumatology/key001] [PMID: 30445483]
[7]
Bartel DP. MicroRNAs: Genomics biogenesis, mechanism and function. Cell 2004; 116(2): 281-97.
[http://dx.doi.org/10.1016/S0092-8674(04)00045-5] [PMID: 14744438]
[8]
Michlewski G, Cáceres JF. Post-transcriptional control of miRNA biogenesis. RNA 2019; 25(1): 1-16.
[http://dx.doi.org/10.1261/rna.068692.118] [PMID: 30333195]
[9]
Qu Z, Li W, Fu B. MicroRNAs in autoimmune diseases. BioMed Res Int 2014; 2014: 1-8.
[http://dx.doi.org/10.1155/2014/527895] [PMID: 24991561]
[10]
Yan L, Liang M, Hou X, et al. The role of microRNA-16 in the pathogenesis of autoimmune diseases: A comprehensive review. Biomed Pharmacother 2019; 112: 108583.
[http://dx.doi.org/10.1016/j.biopha.2019.01.044] [PMID: 30780103]
[11]
Yang H, Chen Y, Xu W, et al. Epigenetics of ankylosing spondylitis: Recent developments. Int J Rheum Dis 2021; 24(4): 487-93.
[http://dx.doi.org/10.1111/1756-185X.14080] [PMID: 33608999]
[12]
Qin X, Zhu B, Jiang T, et al. miR-17-5p regulates heterotopic ossification by targeting ANKH in ankylosing spondylitis. Mol Ther Nucleic Acids 2019; 18: 696-707.
[http://dx.doi.org/10.1016/j.omtn.2019.10.003] [PMID: 31726387]
[13]
Tang SL, Huang QH, Wu LG, Liu C, Cai AL. MiR-124 regulates osteoblast differentiation through GSK-3β in ankylosing spondylitis. Eur Rev Med Pharmacol Sci 2018; 22(20): 6616-24.
[PMID: 30402833]
[14]
Wu Y, Li Q, Zhang R, Dai X, Chen W, Xing D. Circulating microRNAs: Biomarkers of disease. Clin Chim Acta 2021; 516: 46-54.
[http://dx.doi.org/10.1016/j.cca.2021.01.008] [PMID: 33485903]
[15]
Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 1993; 75(5): 843-54.
[http://dx.doi.org/10.1016/0092-8674(93)90529-Y] [PMID: 8252621]
[16]
Lee H, Han S, Kwon CS, Lee D. Biogenesis and regulation of the let-7 miRNAs and their functional implications. Protein Cell 2016; 7(2): 100-13.
[http://dx.doi.org/10.1007/s13238-015-0212-y] [PMID: 26399619]
[17]
Roush S, Slack FJ. The let-7 family of microRNAs. Trends Cell Biol 2008; 18(10): 505-16.
[http://dx.doi.org/10.1016/j.tcb.2008.07.007] [PMID: 18774294]
[18]
Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T. Identification of tissue-specific microRNAs from mouse. Curr Biol 2002; 12(9): 735-9.
[http://dx.doi.org/10.1016/S0960-9822(02)00809-6] [PMID: 12007417]
[19]
Jopling C. Liver-specific microRNA-122: Biogenesis and function. RNA Biol 2012; 9(2): 137-42.
[http://dx.doi.org/10.4161/rna.18827] [PMID: 22258222]
[20]
Rupaimoole R, Slack FJ. MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov 2017; 16(3): 203-22.
[http://dx.doi.org/10.1038/nrd.2016.246] [PMID: 28209991]
[21]
Backes C, Meese E, Keller A. Specific miRNA Disease Biomarkers in Blood, Serum and Plasma: Challenges and Prospects. Mol Diagn Ther 2016; 20(6): 509-18.
[http://dx.doi.org/10.1007/s40291-016-0221-4] [PMID: 27378479]
[22]
Martínez-Ramos S, Rafael-Vidal C, Pego-Reigosa JM, García S. Monocytes and macrophages in spondyloarthritis: Functional roles and effects of current therapies. Cells 2022; 11(3): 515.
[http://dx.doi.org/10.3390/cells11030515] [PMID: 35159323]
[23]
Kumar Kingsley SM, Vishnu Bhat B. Role of MicroRNAs in the development and function of innate immune cells. Int Rev Immunol 2017; 36(3): 154-75.
[http://dx.doi.org/10.1080/08830185.2017.1284212] [PMID: 28471289]
[24]
Mohammadi H, Hemmatzadeh M, Babaie F, et al. MicroRNA implications in the etiopathogenesis of ankylosing spondylitis. J Cell Physiol 2018; 233(8): 5564-73.
[http://dx.doi.org/10.1002/jcp.26500] [PMID: 29377110]
[25]
Wang J, Zhao Q, Wang G, et al. Circulating levels of Th1 and Th2 chemokines in patients with ankylosing spondylitis. Cytokine 2016; 81: 10-4.
[http://dx.doi.org/10.1016/j.cyto.2016.01.012] [PMID: 26827189]
[26]
Zhang CL, Li YC, Wu JW, Zhu BL. Expression and function of peripheral blood miRNA16a in patients with ankylosing spondylitis. Eur Rev Med Pharmacol Sci 2018; 22(16): 5106-13.
[PMID: 30178829]
[27]
Lai N-S, Yu H-C, Chen H-C, Yu C-L, Huang H-B, Lu M-C. Aberrant expression of microRNAs in T cells from patients with ankylosing spondylitis contributes to the immunopathogenesis. Clin Exp Immunol 2013; 173(1): 47-57.
[http://dx.doi.org/10.1111/cei.12089] [PMID: 23607629]
[28]
Chen L, Al-Mossawi MH, Ridley A, et al. miR-10b-5p is a novel Th17 regulator present in Th17 cells from ankylosing spondylitis. Ann Rheum Dis 2017; 76(3): 620-5.
[http://dx.doi.org/10.1136/annrheumdis-2016-210175] [PMID: 28039186]
[29]
Wang M, Wang L, Zhang X, et al. Overexpression of miR-31 in peripheral blood mononuclear cells (PBMC) from patients with ankylosing spondylitis. Med Sci Monit 2017; 23: 5488-94.
[http://dx.doi.org/10.12659/MSM.905238] [PMID: 29150993]
[30]
Motta F, Carena MC, Selmi C, Vecellio M. MicroRNAs in ankylosing spondylitis: Function, potential and challenges. J Transl Autoimmun 2020; 3: 100050.
[http://dx.doi.org/10.1016/j.jtauto.2020.100050] [PMID: 32743531]
[31]
Nusse R, Clevers H. Wnt/β-catenin signaling, disease, and emerging therapeutic modalities. Cell 2017; 169(6): 985-99.
[http://dx.doi.org/10.1016/j.cell.2017.05.016] [PMID: 28575679]
[32]
Du W, Yin L, Tong P, et al. MiR-495 targeting dvl-2 represses the inflammatory response of ankylosing spondylitis. Am J Transl Res 2019; 11(5): 2742-53.
[PMID: 31217850]
[33]
Zhang F, Cao K, Du G, Zhang Q, Yin Z. miR-29a promotes osteoblast proliferation by downregulating DKK-1 expression and activating Wnt/β-catenin signaling pathway. Adv Clin Exp Med 2019; 28(10): 1293-300.
[http://dx.doi.org/10.17219/acem/104533] [PMID: 31538414]
[34]
Li C, Zhang P, Gu J. miR-29a modulates tumor necrosis factor-α-induced osteogenic inhibition by targeting Wnt antagonists. Dev Growth Differ 2015; 57(3): 264-73.
[http://dx.doi.org/10.1111/dgd.12207] [PMID: 25846459]
[35]
Chen G, Deng C, Li YP. TGF-β and BMP signaling in osteoblast differentiation and bone formation. Int J Biol Sci 2012; 8(2): 272-88.
[http://dx.doi.org/10.7150/ijbs.2929] [PMID: 22298955]
[36]
Sánchez-Duffhues G, Hiepen C, Knaus P, Ten Dijke P. Bone morphogenetic protein signaling in bone homeostasis. Bone 2015; 80: 43-59.
[37]
Ding L, Yin Y, Hou Y, et al. microRNA-214-3p suppresses ankylosing spondylitis fibroblast osteogenesis via BMP–TGFβ axis and BMP2. Front Endocrinol 2021; 11: 609753.
[http://dx.doi.org/10.3389/fendo.2020.609753] [PMID: 33935961]
[38]
Zhao J, Zhang Y, Liu B. MicroRNA 204 5p inhibits the osteogenic differentiation of ankylosing spondylitis fibroblasts by regulating the Notch2 signaling pathway. Mol Med Rep 2020; 22(3): 2537-44.
[http://dx.doi.org/10.3892/mmr.2020.11303] [PMID: 32705191]
[39]
Lu Z, Liu M, Stribinskis V, et al. MicroRNA-21 promotes cell transformation by targeting the programmed cell death 4 gene. Oncogene 2008; 27(31): 4373-9.
[http://dx.doi.org/10.1038/onc.2008.72] [PMID: 18372920]
[40]
Huang CH, Wei JCC, Chang WC, et al. Higher expression of whole blood microRNA-21 in patients with ankylosing spondylitis associated with programmed cell death 4 mRNA expression and collagen cross-linked C-telopeptide concentration. J Rheumatol 2014; 41(6): 1104-11.
[http://dx.doi.org/10.3899/jrheum.130515] [PMID: 24786924]
[41]
Xie Z, Li J, Wang P, et al. Differential expression profiles of long noncoding RNA and mRNA of osteogenically differentiated mesenchymal stem cells in ankylosing spondylitis. J Rheumatol 2016; 43(8): 1523-31.
[http://dx.doi.org/10.3899/jrheum.151181] [PMID: 27182066]
[42]
Liu W, Wang P, Xie Z, et al. Abnormal inhibition of osteoclastogenesis by mesenchymal stem cells through the miR-4284/CXCL5 axis in ankylosing spondylitis. Cell Death Dis 2019; 10(3): 188.
[http://dx.doi.org/10.1038/s41419-019-1448-x] [PMID: 30804325]
[43]
Liu Z, Huang F, Luo G, et al. miR-214 stimulated by IL-17A regulates bone loss in patients with ankylosing spondylitis. Rheumatology 2020; 59(5): 1159-69.
[http://dx.doi.org/10.1093/rheumatology/kez594] [PMID: 31846044]
[44]
Hou C, Zhu M, Sun M, Lin Y. MicroRNA let-7i induced autophagy to protect T cell from apoptosis by targeting IGF1R. Biochem Biophys Res Commun 2014; 453(4): 728-34.
[http://dx.doi.org/10.1016/j.bbrc.2014.10.002] [PMID: 25305490]
[45]
Xia Y, Chen K, Zhang MH, et al. MicroRNA-124 involves in ankylosing spondylitis by targeting ANTXR2. Mod Rheumatol 2015; 25(5): 784-9.
[http://dx.doi.org/10.3109/14397595.2015.1023887] [PMID: 25736362]
[46]
Wang Y, Luo J, Wang X, Yang B, Cui L. MicroRNA-199a-5p induced autophagy and inhibits the pathogenesis of ankylosing spondylitis by modulating the mTOR signaling via directly targeting ras homolog enriched in brain (Rheb). Cell Physiol Biochem 2017; 42(6): 2481-91.
[47]
Li F, Si D, Guo X, et al. Aberrant expression of miR 130a 3p in ankylosing spondylitis and its role in regulating T cell survival. Mol Med Rep 2019; 20(4): 3388-94.
[http://dx.doi.org/10.3892/mmr.2019.10573] [PMID: 31432140]
[48]
Guangxue G, Yongfeng H, Gang X, et al. RETRACTED: MicroRNA-204-GSDMD interaction regulates pyroptosis of fibroblast-like synoviocytes in ankylosing spondylitis. Int Immunopharmacol 2021; 91: 107227.
[http://dx.doi.org/10.1016/j.intimp.2020.107227] [PMID: 33359850]
[49]
Wielinska J, Bogunia-Kubik K. miRNAs as potential biomarkers of treatment outcome in rheumatoid arthritis and ankylosing spondylitis. Pharmacogenomics 2021; 22(5): 291-301.
[http://dx.doi.org/10.2217/pgs-2020-0148] [PMID: 33769067]
[50]
Fotoh DS, Noreldin RI, Rizk MS, Elsabaawy MM, Esaily HA. miRNA-451a and miRNA-125a expression levels in ankylosing spondylitis: Impact on disease diagnosis, prognosis, and outcomes. J Immunol Res 2020; 2020: 1-8.
[http://dx.doi.org/10.1155/2020/2180913] [PMID: 33426087]
[51]
Ciechomska M, Bonek K, Merdas M, et al. Changes in MiRNA-5196 expression as a potential biomarker of anti-TNF-α therapy in rheumatoid arthritis and ankylosing spondylitis patients. Arch Immunol Ther Exp 2018; 66(5): 389-97.
[http://dx.doi.org/10.1007/s00005-018-0513-y] [PMID: 29744553]
[52]
Di G, Kong L, Zhao Q, Ding T. MicroRNA-146a knockdown suppresses the progression of ankylosing spondylitis by targeting dickkopf 1. Biomed Pharmacother 2018; 97: 1243-9.
[http://dx.doi.org/10.1016/j.biopha.2017.11.067] [PMID: 29145150]
[53]
Zhang Y, Tu B, Sha Q, Qian J. Bone marrow mesenchymal stem cells-derived exosomes suppress miRNA-5189-3p to increase fibroblast-like synoviocyte apoptosis via the BATF2/JAK2/STAT3 signaling pathway. Bioengineered 2022; 13(3): 6767-80.
[http://dx.doi.org/10.1080/21655979.2022.2045844] [PMID: 35246006]
[54]
Zhang X, Ji S, Cai G, et al. H19 increases IL-17A/IL-23 releases via regulating VDR by interacting with miR675-5p/miR22-5p in ankylosing spondylitis. Mol Ther Nucleic Acids 2020; 19: 393-404.
[http://dx.doi.org/10.1016/j.omtn.2019.11.025] [PMID: 31887550]
[55]
Wang T, Meng S, Chen P, et al. Comprehensive analysis of differentially expressed mRNA and circRNA in Ankylosing spondylitis patients’ platelets. Exp Cell Res 2021; 409(1): 112895.
[http://dx.doi.org/10.1016/j.yexcr.2021.112895] [PMID: 34717918]
[56]
Li X, Zhou W, Li Z, Guan F. Hsa_circ_0056558 regulates cyclin-dependent kinase 6 by sponging microRNA-1290 to suppress the proliferation and differentiation in ankylosing spondylitis. Autoimmunity 2021; 54(2): 114-28.
[http://dx.doi.org/10.1080/08916934.2021.1894417] [PMID: 33685301]
[57]
Chen Y, Gao DY, Huang L. In vivo delivery of miRNAs for cancer therapy: Challenges and strategies. Adv Drug Deliv Rev 2015; 81: 128-41.
[http://dx.doi.org/10.1016/j.addr.2014.05.009] [PMID: 24859533]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy