Abstract
Arthritis is a kind of autoimmune disease, which includes many circumstances that affect joints, the tissues surrounding the joints, and other connective tissues. Osteoarthritis (OA) and rheumatoid arthritis (RA) are the common arthritis seen in many populations. Researchers have made extensive studies on all types of arthritis, novel drugs are being developed by many laboratories, but yet no treatment option is available for these diseases and need new insight into the molecular pathways and pathophysiology of all types of arthritis. MicroRNAs (miRNAs), a class of non-coding RNAs, have shown to be played a plenty of roles in both a suppressive and a promoting role in disease pathogenesis and progression. Among the classes of microRNAs, miR-21 is a widespread miRNA commonly upregulated in many diseases and suggesting that it plays an important role in cell proliferation, apoptosis, and invasion. It is highly expressed in osteoclast precursors and the pro-osteoclastogenic nature of miR-21 makes it a promising candidate as a therapeutic target to treat bone-related disorders. Up to now, there are few papers that demonstrate the role of miR-21 in arthritis and related bone disorders and the number of studies related to different types of arthritis is sparse. Therefore, the main thrust of this paper is to provide an overview of the current clinical evidence and significance of miR-21 in arthritis and bone-related inflammation disorders. We summarize the important research findings surrounding the role of miR-21 and its involvement in the treatment of different types of arthritis.
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References
Sambamoorthi U, Shah D, Zhao X (2017) Healthcare burden of depression in adults with arthritis. Expert Rev Pharmacoecon Outcomes Res 17(1):53–65. https://doi.org/10.1080/14737167.2017.1281744
Reginster JY (2002) The prevalence and burden of arthritis. Rheumatology (Oxford) 41(Supp 1):3–6
Thysen S, Luyten FP, Lories RJ (2015) Targets, models and challenges in osteoarthritis research. Dis Model Mech 8(1):17–30. https://doi.org/10.1242/dmm.016881
Matthews GL (2013) Disease modification: promising targets and impediments to success. Rheum Dis Clin N Am 39(1):177–187. https://doi.org/10.1016/j.rdc.2012.10.006
Ding F, You T, Hou XD, Yi K, Liu XG, Zhang P, Wang XK (2019) MiR-21 regulates pulmonary hypertension in rats via TGF-β1/Smad2 signaling pathway. Eur Rev Med Pharmacol Sci 23:3984–3992
Priyanka P, Panagal M, Sivakumar P, Gopinath V, Ananthavalli R, Karthigeyan M et al (2018) Identification, expression, and methylation of miR-7110 and its involvement in type 1 diabetes mellitus. Gene Reports 11:229–234
Dudics S, Venkatesha SH, Moudgil KD (2018) The micro-RNA expression profiles of autoimmune arthritis reveal novel biomarkers of the disease and therapeutic response. Int J Mol Sci 19(8):2293. https://doi.org/10.3390/ijms19082293
Zou QF, Li L, Han QR, Wang YJ, Wang XB (2019) Abatacept alleviates rheumatoid arthritis development by inhibiting migration of fibroblast-like synoviocytes via MAPK pathway. Eur Rev Med Pharmacol Sci 23:3105–3111
Churov AV, Oleinik EK, Knip M (2015) MicroRNAs in rheumatoid arthritis: altered expression and diagnostic potential. Autoimmun Rev 14(11):1029–1037. https://doi.org/10.1016/j.autrev.2015.07.005
Ciancio G, Ferracin M, Saccenti E, Bagnari V, Farina I, Furini F, Galuppi E, Zagatti B, Trotta F, Negrini M, Govoni M (2017) Characterisation of peripheral blood mononuclear cell microRNA in early onset psoriatic arthritis. Clin Exp Rheumatol 35(1):113–121
Madhyastha R, Madhyastha H, Pengjam Y, Nurrahmah QI, Nakajima Y, Maruyama M (2019) The pivotal role of microRNA-21 in osteoclastogenesis inhibition by anthracycline glycoside aloin. J Nat Med 73(1):59–66. https://doi.org/10.1007/s11418-018-1237-3
Chen JQ, Papp G, Póliska S, Szabó K, Tarr T, Bálint BL, Szodoray P, Zeher M (2017) MicroRNA expression profiles identify disease-specific alterations in systemic lupus erythematosus and primary Sjögren’s syndrome. PLoS One 12(3):e0174585. https://doi.org/10.1371/journal.pone.0174585
Jin S, Chen H, Li Y, Zhong H, Sun W, Wang J, Zhang T, Ma J, Yan S, Zhang J, Tian Q, Yang X, Wang J (2018) Maresin 1 improves the Treg/Th17 imbalance in rheumatoid arthritis through miR-21. Ann Rheum Dis 77(11):1644–1652. https://doi.org/10.1136/annrheumdis-2018-213511
Hu SL, Chang AC, Huang CC, Tsai CH, Lin CC, Tang CH (2017) Myostatin promotes interleukin-1β expression in rheumatoid arthritis synovial fibroblasts through inhibition of miR-21-5p. Front Immunol 8:1747. https://doi.org/10.3389/fimmu.2017.01747
Li H, Chen X, Guan L, Qi Q, Shu G, Jiang Q, Yuan L, Xi Q, Zhang Y (2013) MiRNA-181a regulates adipogenesis by targeting tumor necrosis factor-α (TNF-α) in the porcine model. PLoS One 8(10):e71568. https://doi.org/10.1371/journal.pone.0071568
Zhang J, Jia J, Zhao L, Li X, Xie Q, Chen X, Wang J, Lu F (2016) Down-regulation of microRNA-9 leads to activation of IL-6/Jak/STAT3 pathway through directly targeting IL-6 in HeLa cell. Mol Carcinog 55(5):732–742. https://doi.org/10.1002/mc.22317
Yuan Y, Zhang GQ, Chai W, Ni M, Xu C, Chen JY (2016) Silencing of microRNA-138-5p promotes IL-1β-induced cartilage degradation in human chondrocytes by targeting FOXC1: miR-138 promotes cartilage degradation. Bone Joint Res 5(10):523–530. https://doi.org/10.1302/2046-3758.510.BJR-2016-0074.R2
Elmesmari A, Fraser AR, Wood C, Gilchrist D, Vaughan D, Stewart L, McSharry C, McInnes IB, Kurowska-Stolarska M (2016) MicroRNA-155 regulates monocyte chemokine and chemokine receptor expression in Rheumatoid Arthritis. Rheumatology (Oxford) 55(11):2056–2065. https://doi.org/10.1093/rheumatology/kew272
Wang H, Peng W, Ouyang X, Li W, Dai Y (2012) Circulating microRNAs as candidate biomarkers in patients with systemic lupus erythematosus. Transl Res 160(3):198–206. https://doi.org/10.1016/j.trsl.2012.04.002
Smigielska-Czepiel K, van den Berg A, Jellema P, van der Lei RJ, Bijzet J, Kluiver J, Boots AM, Brouwer E, Kroesen BJ (2014) Comprehensive analysis of miRNA expression in T-cell subsets of rheumatoid arthritis patients reveals defined signatures of naive and memory Tregs. Genes Immun 15(2):115–125. https://doi.org/10.1038/gene.2013.69
Chen Y, Xian PF, Yang L, Wang SX (2016) MicroRNA-21 promotes proliferation of fibroblast-like synoviocytes through mediation of NF-κB nuclear translocation in a rat model of collagen-induced rheumatoid arthritis. Biomed Res Int 2016:9279078. https://doi.org/10.1155/2016/9279078
Yang S, Jiang S, Wang Y, Tu S, Wang Z, Chen Z (2016) Interleukin 34 upregulation contributes to the increment of microRNA 21 expression through STAT3 activation associated with disease activity in rheumatoid arthritis. J Rheumatol 43(7):1312–1319. https://doi.org/10.3899/jrheum.151253
Dong L, Wang X, Tan J, Li H, Qian W, Chen J, Chen Q, Wang J, Xu W, Tao C, Wang S (2014) Decreased expression of microRNA-21 correlates with the imbalance of Th17 and Treg cells in patients with rheumatoid arthritis. J Cell Mol Med 18(11):2213–2224. https://doi.org/10.1111/jcmm.12353
Iliopoulos D, Kavousanaki M, Ioannou M, Boumpas D, Verginis P (2011) The negative costimulatory molecule PD-1 modulates the balance between immunity and tolerance via miR-21. Eur J Immunol 41(6):1754–1763. https://doi.org/10.1002/eji.201040646
Balzano F, Deiana M, Dei Giudici S, Oggiano A, Pasella S, Pinna S, Mannu A, Deiana N, Porcu B, Masala A, Pileri PV, Scognamillo F, Pala C, Zinellu A, Carru C, Deiana L (2017) MicroRNA expression analysis of centenarians and rheumatoid arthritis patients reveals a common expression pattern. Int J Med Sci 14(7):622–628. https://doi.org/10.7150/ijms.18972
Liu XG, Zhang Y, Ju WF, Li CY, Mu YC (2019) MiR-21 relieves rheumatoid arthritis in rats via targeting Wnt signaling pathway. Eur Rev Med Pharmacol Sci 23(3 Suppl):96–103. https://doi.org/10.26355/eurrev_201908_18635
Huang R-Y, Wu J-Q, Liu Z-H, Sun S-L (2019) MicroRNAs in rheumatoid arthritis: what is the latest with regards to diagnostics? Expert Rev Mol Diagn 19(5):363–366. https://doi.org/10.1080/14737159.2019.1599716
Tsezou A (2014) Osteoarthritis year in review 2014: genetics and genomics. Osteoarthr Cartil 22(12):2017–2024. https://doi.org/10.1016/j.joca.2014.07.024
Song J, Ahn C, Chun CH, Jin EJ (2014) A long non-coding RNA, GAS5, plays a critical role in the regulation of miR-21 during osteoarthritis. J Orthop Res 32(12):1628–1635. https://doi.org/10.1002/jor.22718
Song J, Lee M, Kim D, Han J, Chun CH, Jin EJ (2013) MicroRNA-181b regulates articular chondrocytes differentiation and cartilage integrity. Biochem Biophys Res Commun 431(2):210–214. https://doi.org/10.1016/j.bbrc.2012.12.133
Miyaki S, Asahara H (2012) Macro view of microRNA function in osteoarthritis. Nat Rev Rheumatol 8(9):543–552. https://doi.org/10.1038/nrrheum.2012.128
Harfe BD, McManus MT, Mansfield JH, Hornstein E, Tabin CJ (2005) The RNaseIII enzyme Dicer is required for morphogenesis but not patterning of the vertebrate limb. Proc Natl Acad Sci U S A 102(31):10898–10903. https://doi.org/10.1073/pnas.0504834102
Kobayashi T, Lu J, Cobb BS, Rodda SJ, McMahon AP, Schipani E, Merkenschlager M, Kronenberg HM (2008) Dicer-dependent pathways regulate chondrocyte proliferation and differentiation. Proc Natl Acad Sci U S A 105(6):1949–1954. https://doi.org/10.1073/pnas.0707900105
Mizoguchi F, Izu Y, Hayata T, Hemmi H, Nakashima K, Nakamura T, Kato S, Miyasaka N, Ezura Y, Noda M (2010) Osteoclast-specific Dicer gene deficiency suppresses osteoclastic bone resorption. J Cell Biochem 109(5):866–875. https://doi.org/10.1002/jcb.22228
Zhang Y, Jia J, Yang S, Liu X, Ye S, Tian H (2014) MicroRNA-21 controls the development of osteoarthritis by targeting GDF-5 in chondrocytes. Exp Mol Med 46(2):e79. https://doi.org/10.1038/emm.2013.152
Figueiredo Neto M, Figueiredo ML (2017) Combination of interleukin-27 and microRNA for enhancing expression of anti-inflammatory and proosteogenic genes. Arthritis 2017:6365857. https://doi.org/10.1155/2017/6365857
Li HW, Xie Y, Li F, Sun GC, Chen Z, Zeng HS (2016) Effect of miR-19a and miR-21 on the JAK/STAT signaling pathway in the peripheral blood mononuclear cells of patients with systemic juvenile idiopathic arthritis. Exp Ther Med 11(6):2531–2536. https://doi.org/10.3892/etm.2016.3188
Wu XN, Ye YX, Niu JW, Li Y, Li X, You X, Chen H, Zhao LD, Zeng XF, Zhang FC, Tang FL, He W, Cao XT, Zhang X, Lipsky PE (2014) Defective PTEN regulation contributes to B cell hyperresponsiveness in systemic lupus erythematosus. Sci Transl Med 6(246):246ra99. https://doi.org/10.1126/scitranslmed.3009131
Fogel O, Bugge Tinggaard A, Fagny M, Sigrist N, Roche E, Leclere L, Deleuze JF, Batteux F, Dougados M, Miceli-Richard C, Tost J (2019) Deregulation of microRNA expression in monocytes and CD4+ T lymphocytes from patients with axial spondyloarthritis. Arthritis Res Ther 21(1):51. https://doi.org/10.1186/s13075-019-1829-7
Motta F, Carena MC, Selmi C, Vecellio M (2020) MicroRNAs in Ankylosing Spondylitis: function, potential and challenges. J Transl Autoimmun 3:100050. https://doi.org/10.1016/j.jtauto.2020.100050
Hoshikawa N, Sakai A, Takai S, Suzuki H (2020) Targeting extracellular miR-21-TLR7 signaling provides long lasting analgesia in Osteosrthritis. Mol Ther Nucleic Acids 19:199–207
Zhu H, Yan X, Zhang M, Ji F, Wang S (2019) miR-21-5p protects IL-1β-induced human chondrocytes from degradation. J Orthop Surg Res 14(1):118. https://doi.org/10.1186/s13018-019-1160-7
Wang XB, Zhao FC, Yi LH, Tang JL, Zhu ZY, Pang Y, Chen YS, Li DY, Guo KJ, Zheng X (2019) MicroRNA-21-5p as a novel therapeutic target for osteoarthritis. Rheumatology (Oxford):kez102. Advance online publication. https://doi.org/10.1093/rheumatology/kez102
Ma S, Zhang A, Li X, Zhang S, Liu S, Zhao H, Wu S, Chen L, Ma C, Zhao H (2020) MiR-21-5p regulates extracellular matrix degradation and angiogenesis in TMJOA by targeting Spry1. Arthritis Res Ther 22(1):99. https://doi.org/10.1186/s13075-020-2145-y
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Sekar, D. Implications of microRNA 21 and its involvement in the treatment of different type of arthritis. Mol Cell Biochem 476, 941–947 (2021). https://doi.org/10.1007/s11010-020-03960-y
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DOI: https://doi.org/10.1007/s11010-020-03960-y