The Therapeutic Potential and Role of miRNA, lncRNA, and circRNA in Osteoarthritis

Author(s): Yuangang Wu, Xiaoxi Lu, Bin Shen, Yi Zeng*

Journal Name: Current Gene Therapy

Volume 19 , Issue 4 , 2019

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Abstract:

Background: Osteoarthritis (OA) is a disease characterized by progressive degeneration, joint hyperplasia, narrowing of joint spaces, and extracellular matrix metabolism. Recent studies have shown that the pathogenesis of OA may be related to non-coding RNA, and its pathological mechanism may be an effective way to reduce OA.

Objective: The purpose of this review was to investigate the recent progress of miRNA, long noncoding RNA (lncRNA) and circular RNA (circRNA) in gene therapy of OA, discussing the effects of this RNA on gene expression, inflammatory reaction, apoptosis and extracellular matrix in OA.

Methods: The following electronic databases were searched, including PubMed, EMBASE, Web of Science, and the Cochrane Library, for published studies involving the miRNA, lncRNA, and circRNA in OA. The outcomes included the gene expression, inflammatory reaction, apoptosis, and extracellular matrix.

Results and Discussion: With the development of technology, miRNA, lncRNA, and circRNA have been found in many diseases. More importantly, recent studies have found that RNA interacts with RNA-binding proteins to regulate gene transcription and protein translation, and is involved in various pathological processes of OA, thus becoming a potential therapy for OA.

Conclusion: In this paper, we briefly introduced the role of miRNA, lncRNA, and circRNA in the occurrence and development of OA and as a new target for gene therapy.

Keywords: Osteoarthritis, miRNA, lncRNA, circRNA, new target, gene therapy.

[1]
Thomas AC, Hubbard-Turner T, Wikstrom EA, Palmieri-Smith RM. Epidemiology of posttraumatic osteoarthritis. J Athl Train 2017; 52(6): 491-6.
[http://dx.doi.org/10.4085/1062-6050-51.5.08] [PMID: 27145096]
[2]
Flemming DJ, Gustas-French CN. Rapidly progressive osteoarthritis: A review of the clinical and radiologic presentation. Curr Rheumatol Rep 2017; 19(7): 42.
[http://dx.doi.org/10.1007/s11926-017-0665-5] [PMID: 28689367]
[3]
Litwic A, Edwards MH, Dennison EM, Cooper C. Epidemiology and burden of osteoarthritis. Br Med Bull 2013; 105: 185-99.
[http://dx.doi.org/10.1093/bmb/lds038] [PMID: 23337796]
[4]
Malemud CJ. MicroRNAs and osteoarthritis. Cells 2018; 7(8)E92
[http://dx.doi.org/10.3390/cells7080092] [PMID: 30071609]
[5]
Musumeci G, Castrogiovanni P, Trovato FM, et al. Biomarkers of chondrocyte apoptosis and autophagy in osteoarthritis. Int J Mol Sci 2015; 16(9): 20560-75.
[http://dx.doi.org/10.3390/ijms160920560] [PMID: 26334269]
[6]
Sun H, Peng G, Ning X, Wang J, Yang H, Deng J. Emerging roles of long noncoding RNA in chondrogenesis, osteogenesis, and osteoarthritis. Am J Transl Res 2019; 11(1): 16-30.
[PMID: 30787967]
[7]
Li HZ, Lin Z, Xu XH, Lin N, Lu HD. The potential roles of circRNAs in osteoarthritis: A coming journey to find a treasure. Biosci Rep 2018; 38(5)BSR20180542
[http://dx.doi.org/10.1042/BSR20180542] [PMID: 30279209]
[8]
Li L, Zhuang Y, Zhao X, Li X. Long non-coding RNA in neuronal development and neurological disorders. Front Genet 2019; 9: 744.
[http://dx.doi.org/10.3389/fgene.2018.00744] [PMID: 30728830]
[9]
Bahiraee A, Ebrahimi R, Halabian R, Aghabozorgi AS, Amani J. The role of inflammation and its related microRNAs in breast cancer: A narrative review. J Cell Physiol 2019. Epub ahead of print
[http://dx.doi.org/10.1002/jcp.28742] [PMID: 31025369]
[10]
Soroosh A, Koutsioumpa M, Pothoulakis C, Iliopoulos D. Functional role and therapeutic targeting of microRNAs in inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 2018; 314(2): G256-62.
[http://dx.doi.org/10.1152/ajpgi.00268.2017] [PMID: 29146677]
[11]
Ma Y, Wu Y, Chen J, et al. miR-10a-5p Promotes chondrocyte apoptosis in osteoarthritis by targeting HOXA1. Mol Ther Nucleic Acids 2019; 14: 398-409.
[http://dx.doi.org/10.1016/j.omtn.2018.12.012] [PMID: 30731321]
[12]
Soyocak A, Kurt H, Ozgen M, Turgut CD, Colak E, Gunes HV. miRNA-146a, miRNA-155 and JNK expression levels in peripheral blood mononuclear cells according to grade of knee osteoarthritis. Gene 2017; 627: 207-11.
[http://dx.doi.org/10.1016/j.gene.2017.06.027] [PMID: 28647559]
[13]
Ding Y, Wang L, Zhao Q, Wu Z, Kong L. MicroRNA-93 inhibits chondrocyte apoptosis and inflammation in osteoarthritis by targeting the TLR4/NF-κB signaling pathway. Int J Mol Med 2019; 43(2): 779-90.
[PMID: 30569118]
[14]
Liu J, Yu Q, Ye Y, Yan Y, Chen X. Abnormal expression of miR-4784 in chondrocytes of osteoarthritis and associations with chondrocyte hyperplasia. Exp Ther Med 2018; 16(6): 4690-4.
[http://dx.doi.org/10.3892/etm.2018.6739] [PMID: 30542421]
[15]
Yang X, Zhang Q, Gao Z, Yu C, Zhang L. Down-Regulation of MiR-150 alleviates inflammatory injury induced by interleukin 1 via targeting Kruppel-Like Factor 2 in human chondrogenic cells. Cell Physiol Biochem 2018; 47(6): 2579-88.
[http://dx.doi.org/10.1159/000491654] [PMID: 29996115]
[16]
Ren C, Liang Z. Piperine alleviates lipopolysaccharide-induced inflammatory injury by down-regulating microRNA-127 in murine chondrogenic ATDC5 cells. Biomed Pharmacother 2018; 103: 947-54.
[http://dx.doi.org/10.1016/j.biopha.2018.04.108] [PMID: 29710511]
[17]
Jia J, Wang J, Zhang J, et al. MiR-125b Inhibits LPS-Induced inflammatory injury via targeting MIP-1α in chondrogenic cell ATDC5. Cell Physiol Biochem 2018; 45(6): 2305-16.
[http://dx.doi.org/10.1159/000488178] [PMID: 29550827]
[18]
Zhang W, Zhong B, Zhang C, Luo C, Zhan Y. miR-373 regulates inflammatory cytokine-mediated chondrocyte proliferation in osteoarthritis by targeting the P2X7 receptor. FEBS Open Bio 2018; 8(3): 325-31.
[http://dx.doi.org/10.1002/2211-5463.12345] [PMID: 29511609]
[19]
Wang Y, Yu T, Jin H, Zhao C, Wang Y. Knockdown MiR-302b alleviates LPS-Induced injury by targeting smad3 in C28/I2 Chondrocytic Cells. Cell Physiol Biochem 2018; 45(2): 733-43.
[http://dx.doi.org/10.1159/000487165] [PMID: 29414803]
[20]
Zhang W, Cheng P, Hu W, et al. Inhibition of microRNA-384-5p alleviates osteoarthritis through its effects on inhibiting apoptosis of cartilage cells via the NF-κB signaling pathway by targeting SOX9. Cancer Gene Ther 2018; 25(11-12): 326-38.
[http://dx.doi.org/10.1038/s41417-018-0029-y] [PMID: 30057417]
[21]
Zhang W, Hsu P, Zhong B, et al. MiR-34a enhances chondrocyte apoptosis, senescence and facilitates development of osteoarthritis by targeting DLL1 and regulating PI3K/AKT pathway. Cell Physiol Biochem 2018; 48(3): 1304-16.
[http://dx.doi.org/10.1159/000492090] [PMID: 30048987]
[22]
Huang Z, Zhang N, Ma W, Dai X, Liu J. MiR-337-3p promotes chondrocytes proliferation and inhibits apoptosis by regulating PTEN/AKT axis in osteoarthritis. Biomed Pharmacother 2017; 95: 1194-200.
[http://dx.doi.org/10.1016/j.biopha.2017.09.016] [PMID: 28931211]
[23]
Wu J, Zou M, Ping A, Deng Z, Cai L. MicroRNA-449a upregulation promotes chondrocyte extracellular matrix degradation in osteoarthritis. Biomed Pharmacother 2018; 105: 940-6.
[http://dx.doi.org/10.1016/j.biopha.2018.06.074] [PMID: 30021388]
[24]
Li C, Hu Q, Chen Z, et al. MicroRNA-140 suppresses human chondrocytes hypertrophy by targeting SMAD1 and controlling the bone morphogenetic protein pathway in osteoarthritis. Am J Med Sci 2018; 355(5): 477-87.
[http://dx.doi.org/10.1016/j.amjms.2018.01.004] [PMID: 29753378]
[25]
Li X, He P, Li Z, et al. Interleukin-1β-mediated suppression of microRNA-27a-3p activity in human cartilage via MAPK and NF-κB pathways: A potential mechanism of osteoarthritis pathogenesis. Mol Med Rep 2018; 18(1): 541-9.
[http://dx.doi.org/10.3892/mmr.2018.8970] [PMID: 29749508]
[26]
Shi J, Guo K, Su S, Li J, Li C. miR-486-5p is upregulated in osteoarthritis and inhibits chondrocyte proliferation and migration by suppressing SMAD2. Mol Med Rep 2018; 18(1): 502-8.
[http://dx.doi.org/10.3892/mmr.2018.8931] [PMID: 29749497]
[27]
Ko JY, Lee MS, Lian WS, et al. MicroRNA-29a counteracts synovitis in knee osteoarthritis pathogenesis by targeting VEGF. Sci Rep 2017; 7(1): 3584.
[http://dx.doi.org/10.1038/s41598-017-03616-w] [PMID: 28620193]
[28]
Baek D, Lee KM, Park KW, et al. Inhibition of miR-449a promotes cartilage regeneration and prevents progression of osteoarthritis in in vivo rat models. Mol Ther Nucleic Acids 2018; 13: 322-33.
[http://dx.doi.org/10.1016/j.omtn.2018.09.015] [PMID: 30326428]
[29]
Cao J, Han X, Qi X, Jin X, Li X. miR-204-5p inhibits the occurrence and development of osteoarthritis by targeting Runx2. Int J Mol Med 2018; 42(5): 2560-8.
[http://dx.doi.org/10.3892/ijmm.2018.3811] [PMID: 30106092]
[30]
Zhang Y, Xu S, Huang E, et al. MicroRNA-130a regulates chondrocyte proliferation and alleviates osteoarthritis through PTEN/PI3K/Akt signaling pathway. Int J Mol Med 2018; 41(6): 3699-708.
[http://dx.doi.org/10.3892/ijmm.2018.3551] [PMID: 29532889]
[31]
Chen Q, Wu S, Wu Y, Chen L, Pang Q. MiR-149 suppresses the inflammatory response of chondrocytes in osteoarthritis by down-regulating the activation of TAK1/NF-κB. Biomed Pharmacother 2018; 101: 763-8.
[http://dx.doi.org/10.1016/j.biopha.2018.02.133] [PMID: 29524885]
[32]
Yang H, Wu D, Li H, Chen N, Shang Y. Downregulation of microRNA-448 inhibits IL-1β-induced cartilage degradation in human chondrocytes via upregulation of matrilin-3. Cell Mol Biol Lett 2018; 23: 7.
[http://dx.doi.org/10.1186/s11658-018-0072-6] [PMID: 29483929]
[33]
Peng H, Liang D, Li B, Liang C, Huang W, Lin H. MicroRNA-320a protects against osteoarthritis cartilage degeneration by regulating the expressions of BMI-1 and RUNX2 in chondrocytes. Pharmazie 2017; 72(4): 223-6.
[PMID: 29441992]
[34]
Li H, Miao D, Zhu Q, Huang J, Lu G, Xu W. MicroRNA-17-5p contributes to osteoarthritis progression by binding p62/SQSTM1. Exp Ther Med 2018; 15(2): 1789-94.
[PMID: 29434766]
[35]
Yu C, Wang Y. MicroRNA-19a promotes cell viability and migration of chondrocytes via up-regulating SOX9 through NF-κB pathway. Biomed Pharmacother 2018; 98: 746-53.
[http://dx.doi.org/10.1016/j.biopha.2017.11.132] [PMID: 29306212]
[36]
Hu J, Wang Z, Pan Y, et al. MiR-26a and miR-26b mediate osteoarthritis progression by targeting FUT4 via NF-κB signaling pathway. Int J Biochem Cell Biol 2018; 94: 79-88.
[http://dx.doi.org/10.1016/j.biocel.2017.12.003] [PMID: 29208566]
[37]
Sun T, Li X, Song H, et al. MiR-146a Aggravates LPS-Induced inflammatory injury by targeting CXCR4 in the articular chondrocytes. Cell Physiol Biochem 2017; 44(4): 1282-94.
[http://dx.doi.org/10.1159/000485488] [PMID: 29183039]
[38]
He W, Cheng Y. Inhibition of miR-20 promotes proliferation and autophagy in articular chondrocytes by PI3K/AKT/mTOR signaling pathway. Biomed Pharmacother 2018; 97: 607-15.
[http://dx.doi.org/10.1016/j.biopha.2017.10.152] [PMID: 29101804]
[39]
Wu DP, Zhang JL, Wang JY, et al. MiR-1246 promotes LPS-induced inflammatory injury in chondrogenic cells ATDC5 by targeting HNF4γ. Cell Physiol Biochem 2017; 43(5): 2010-21.
[http://dx.doi.org/10.1159/000484162] [PMID: 29055957]
[40]
Xu R, Li J, Wei B, Huo W, Wang L. MicroRNA-483-5p modulates the expression of cartilage-related genes in human chondrocytes through down-regulating TGF-β1 expression. Tohoku J Exp Med 2017; 243(1): 41-8.
[http://dx.doi.org/10.1620/tjem.243.41] [PMID: 28924102]
[41]
Wang X, Guo Y, Wang C, Yu H, Yu X, Yu H. MicroRNA-142-3p inhibits chondrocyte apoptosis and inflammation in osteoarthritis by targeting HMGB1. Inflammation 2016; 39(5): 1718-28.
[http://dx.doi.org/10.1007/s10753-016-0406-3] [PMID: 27447821]
[42]
Zhang G, Sun Y, Wang Y, Liu R, Bao Y, Li Q. MiR-502-5p inhibits IL-1β-induced chondrocyte injury by targeting TRAF2. Cell Immunol 2016; 302: 50-7.
[http://dx.doi.org/10.1016/j.cellimm.2016.01.007] [PMID: 26861148]
[43]
Zhang D, Cao X, Li J, Zhao G. MiR-210 inhibits NF-κB signaling pathway by targeting DR6 in osteoarthritis. Sci Rep 2015; 5: 12775.
[http://dx.doi.org/10.1038/srep12775] [PMID: 26244598]
[44]
Xiao Y, Yan X, Yang Y, Ma X. Downregulation of long noncoding RNA HOTAIRM1 variant 1 contributes to osteoarthritis via regulating miR-125b/BMPR2 axis and activating JNK/MAPK/ERK pathway. Biomed Pharmacother 2019; 109: 1569-77.
[http://dx.doi.org/10.1016/j.biopha.2018.10.181] [PMID: 30551410]
[45]
Zheng J, Li Q. Methylene blue regulates inflammatory response in osteoarthritis by noncoding long chain RNA CILinc02. J Cell Biochem 2019; 120(3): 3331-8.
[PMID: 30548658]
[46]
Yang DW, Zhang X, Qian GB, Jiang MJ, Wang P, Wang KZ. Downregulation of long noncoding RNA LOC101928134 inhibits the synovial hyperplasia and cartilage destruction of osteoarthritis rats through the activation of the Janus kinase/signal transducers and activators of transcription signaling pathway by upregulating IFNA1. J Cell Physiol 2019; 234(7): 10523-34.
[http://dx.doi.org/10.1002/jcp.27730] [PMID: 30456844]
[47]
Li X, Yu M, Chen L, et al. LncRNA PMS2L2 protects ATDC5 chondrocytes against lipopolysaccharide-induced inflammatory injury by sponging miR-203. Life Sci 2019; 217: 283-92.
[http://dx.doi.org/10.1016/j.lfs.2018.12.020] [PMID: 30550887]
[48]
Tang L, Ding J, Zhou G, Liu Z. LncRNA-p21 promotes chondrocyte apoptosis in osteoarthritis by acting as a sponge for miR-451. Mol Med Rep 2018; 18(6): 5295-301.
[http://dx.doi.org/10.3892/mmr.2018.9506] [PMID: 30272288]
[49]
Ye D, Jian W, Feng J, Liao X. Role of long noncoding RNA ZFAS1 in proliferation, apoptosis and migration of chondrocytes in osteoarthritis. Biomed Pharmacother 2018; 104: 825-31.
[http://dx.doi.org/10.1016/j.biopha.2018.04.124] [PMID: 29703568]
[50]
Hu J, Wang Z, Shan Y, Pan Y, Ma J, Jia L. Long non-coding RNA HOTAIR promotes osteoarthritis progression via miR-17-5p/FUT2/β-catenin axis. Cell Death Dis 2018; 9(7): 711.
[http://dx.doi.org/10.1038/s41419-018-0746-z] [PMID: 29907764]
[51]
Li YF, Li SH, Liu Y, Luo YT. Long noncoding RNA CIR Promotes chondrocyte extracellular matrix degradation in osteoarthritis by acting as a sponge for Mir-27b. Cell Physiol Biochem 2017; 43(2): 602-10.
[http://dx.doi.org/10.1159/000480532] [PMID: 28934732]
[52]
Pan L, Liu D, Zhao L, Wang L, Xin M, Li X. Long noncoding RNA MALAT1 alleviates lipopolysaccharide-induced inflammatory injury by upregulating microRNA-19b in murine chondrogenic ATDC5 cells. J Cell Biochem 2018; 119(12): 10165-75.
[http://dx.doi.org/10.1002/jcb.27357] [PMID: 30145831]
[53]
Cao L, Wang Y, Wang Q, Huang J. LncRNA FOXD2-AS1 regulates chondrocyte proliferation in osteoarthritis by acting as a sponge of miR-206 to modulate CCND1 expression. Biomed Pharmacother 2018; 106: 1220-6.
[http://dx.doi.org/10.1016/j.biopha.2018.07.048] [PMID: 30119190]
[54]
Li L, Lv G, Wang B, Kuang L. The role of lncRNA XIST/miR-211 axis in modulating the proliferation and apoptosis of osteoarthritis chondrocytes through CXCR4 and MAPK signaling. Biochem Biophys Res Commun 2018; 503(4): 2555-62.
[http://dx.doi.org/10.1016/j.bbrc.2018.07.015] [PMID: 30005876]
[55]
Fan X, Yuan J, Xie J, et al. Long non-protein coding RNA DANCR functions as a competing endogenous RNA to regulate osteoarthritis progression via miR-577/SphK2 axis. Biochem Biophys Res Commun 2018; 500(3): 658-64.
[http://dx.doi.org/10.1016/j.bbrc.2018.04.130] [PMID: 29678573]
[56]
Li F, Sun J, Huang S, Su G, Pi G. LncRNA GAS5 Overexpression reverses LPS-Induced inflammatory injury and apoptosis through Up-Regulating KLF2 expression in ATDC5 Chondrocytes. Cell Physiol Biochem 2018; 45(3): 1241-51.
[http://dx.doi.org/10.1159/000487455] [PMID: 29448248]
[57]
Sun T, Yu J, Han L, et al. Knockdown of long non-coding RNA RP11-445H22.4 alleviates LPS-induced injuries by regulation of MiR-301a in osteoarthritis. Cell Physiol Biochem 2018; 45(2): 832-43.
[http://dx.doi.org/10.1159/000487175] [PMID: 29414810]
[58]
Shen H, Wang Y, Shi W, Sun G, Hong L, Zhang Y. LncRNA SNHG5/miR-26a/SOX2 signal axis enhances proliferation of chondrocyte in osteoarthritis. Acta Biochim Biophys Sin (Shanghai) 2018; 50(2): 191-8.
[http://dx.doi.org/10.1093/abbs/gmx141] [PMID: 29409014]
[59]
Li Y, Li S, Luo Y, Liu Y, Yu N. LncRNA PVT1 Regulates chondrocyte apoptosis in osteoarthritis by acting as a sponge for miR-488-3p. DNA Cell Biol 2017; 36(7): 571-80.
[http://dx.doi.org/10.1089/dna.2017.3678] [PMID: 28520497]
[60]
Su W, Xie W, Shang Q, Su B. The long noncoding RNA MEG3 is downregulated and inversely associated with VEGF levels in osteoarthritis. BioMed Res Int 2015; 2015356893
[http://dx.doi.org/10.1155/2015/356893] [PMID: 26090403]
[61]
Zhou ZB, Huang GX, Fu Q, et al. circRNA.33186 contributes to the pathogenesis of osteoarthritis by sponging miR-127-5p. Mol Ther 2019; 27(3): 531-41.
[http://dx.doi.org/10.1016/j.ymthe.2019.01.006] [PMID: 30692016]
[62]
Wu Y, Zhang Y, Zhang Y, Wang JJ. CircRNA hsa_circ_0005105 upregulates NAMPT expression and promotes chondrocyte extracellular matrix degradation by sponging miR-26a. Cell Biol Int 2017; 41(12): 1283-9.
[http://dx.doi.org/10.1002/cbin.10761] [PMID: 28276108]
[63]
Liu Q, Zhang X, Hu X, et al. Circular RNA related to the chondrocyte ECM regulates MMP13 expression by functioning as a MiR-136 ‘Sponge’ in human cartilage degradation. Sci Rep 2016; 6: 22572.
[http://dx.doi.org/10.1038/srep22572] [PMID: 26931159]
[64]
Zhou ZB, Du D, Huang GX, Chen A, Zhu L. Circular RNA Atp9b, a competing endogenous RNA, regulates the progression of osteoarthritis by targeting miR-138-5p. Gene 2018; 646: 203-9.
[http://dx.doi.org/10.1016/j.gene.2017.12.064] [PMID: 29305974]
[65]
Li BF, Zhang Y, Xiao J, et al. Hsa_circ_0045714 regulates chondrocyte proliferation, apoptosis and extracellular matrix synthesis by promoting the expression of miR-193b target gene IGF1R. Hum Cell 2017; 30(4): 311-8.
[http://dx.doi.org/10.1007/s13577-017-0177-7] [PMID: 28795385]


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VOLUME: 19
ISSUE: 4
Year: 2019
Page: [255 - 263]
Pages: 9
DOI: 10.2174/1566523219666190716092203
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