miRNA与骨关节炎病理发展过程的相关性
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摘要
背景:越来越多的研究表明,mi RNA在骨关节炎的病理发展过程中起着重要调控作用。目的:综述miRNA与骨关节炎病理发展过程的相关性。方法:应用计算机检索CNKI、PubMed等数据库建库至2018年12月有关mi RNA与骨关节炎相关性研究的文献,中文关键词为"骨关节炎,微小RNA",英文关键词为"osteoarthritis,miRNA",进行全文检索。结果与结论:mi RNA与骨关节炎病理发展过程密切相关;miRNA异常表达参与了骨关节炎软骨细胞增殖、凋亡、关节软骨细胞外基质稳态、软骨细胞炎症及关节疼痛;异常表达的mi RNA可作为骨关节炎早期诊断的标志物;miRNA作为一种调控基因在骨关节炎分子靶向治疗中具有广阔的应用前景。
BACKGROUND: More and more studies have shown that miRNA plays an important regulatory role in the pathological development of osteoarthritis.OBJECTIVE: To review the correlation between miRNA and the pathological development of osteoarthritis.METHODS: A computer-based search of CNKI and PubMed databases was conducted for the articles concerning miRNA and osteoarthritis published before December 2018. The keywords were "osteoarthritis, miRNA" in Chinese and English, respectively.RESULTS AND CONCLUSION: miRNA is closely related to the pathogenesis of osteoarthritis. Abnormal expression of miRNA is involved in chondrocyte proliferation and apoptosis, articular cartilage extracellular matrix homeostasis, chondrocyte inflammation and joint pain in osteoarthritis. Abnormally expressed miRNA can be used as a marker for early diagnosis of osteoarthritis. As a regulatory gene, miRNA has broad prospects in molecular targeted therapy of osteoarthritis.
BACKGROUND: More and more studies have shown that miRNA plays an important regulatory role in the pathological development of osteoarthritis.OBJECTIVE: To review the correlation between miRNA and the pathological development of osteoarthritis.METHODS: A computer-based search of CNKI and PubMed databases was conducted for the articles concerning miRNA and osteoarthritis published before December 2018. The keywords were "osteoarthritis, miRNA" in Chinese and English, respectively.RESULTS AND CONCLUSION: miRNA is closely related to the pathogenesis of osteoarthritis. Abnormal expression of miRNA is involved in chondrocyte proliferation and apoptosis, articular cartilage extracellular matrix homeostasis, chondrocyte inflammation and joint pain in osteoarthritis. Abnormally expressed miRNA can be used as a marker for early diagnosis of osteoarthritis. As a regulatory gene, miRNA has broad prospects in molecular targeted therapy of osteoarthritis.
引文
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[3]Kopańska M,Szala D,Czech J,et al.MiRNA expression in the cartilage of patients with osteoarthritis.J Orthop Surg Res.2017;12(1):51.
[4]Aigner T,S?der S,Gebhard PM,et al.Mechanisms of Disease:role of chondrocytes in the pathogenesis of osteoarthritisstructure,chaos and senescence.Nat Clin Pract Rheumatol.2007;3(7):391-399.
[5]Le LT,Swingler TE,Clark IM.Review:the role of microRNAs in osteoarthritis and chondrogenesis.Arthritis Rheum.2013;65(8):1963-1974.
[6]Beyer C,Zampetaki A,Lin NY,et al.Signature of circulating microRNAs in osteoarthritis.Ann Rheum Dis.2015;74(3):e18.
[7]Cannell IG,Kong YW,Bushell M.How do microRNAs regulate gene expression?Biochem Soc Trans.2008;36:1224-1231.
[8]Ha M,Kim VN.Regulation of microRNA biogenesis.Nat Rev Mol Cell Biol.2014;15(8):509-524.
[9]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):843-854.
[10]Reinhart BJ,Slack FJ,Basson M.The 21-nucleotide let-7 RNAregulates developmental timing in Caenorhabditis elegans.Nature.2000;403(6772):901-906.
[11]Farh KK,Grimson A,Jan C,et al.The widespread impact of mammalian MicroRNAs on mRNA repression and evolution.Science.2005;310(5755):1817-1821.
[12]马圣运,白玉,韩凝,等.miRNA生物合成及其功能研究的新发现[J].遗传,2012,34(4):5-10.
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[14]Zeng Y,Cullen BR.Structural requirements for premicroRNAbinding and nuclear export by Exportin 5.Nucleic Acids Res.2004;32(16):4776-4785.
[15]Rhoades MW,Reinhart BJ,Lim LP,et al.Prediction of plant microRNA targets.Cell.2002;110(4):513-520.
[16]Chen X.MicroRNA biogenesis and function in plants.FEBSLett.2005;579(26):5923-5931.
[17]Smalheiser NR,Torvik VI.Complications in mammalian microRNA target prediction.Methods Mol Biol.2006;342:115-127.
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[20]van der Kraan PM,van den Berg WB.Chondrocyte hypertrophy and osteoarthritis:role in initiation and progression of cartilage degeneration?Osteoarthritis Cartilage.2012;20(3):223-232.
[21]Nielsen FK,Egund N,J?rgensen A,et al.Risk factors for joint replacement in knee osteoarthritis;a 15-year follow-up study.BMC MusculoskeletDisord.2017;18(1):510.
[22]Duarte N,Rodrigues AM,Branco JDC,et al.Health and Lifestyles Factors Associated With Osteoarthritis among Older Adults in Portugal.Front Med(Lausanne).2017;4:192.
[23]Yan S,Wang M,Zhao J,et al.MicroRNA-34a affects chondrocyte apoptosis and proliferation by targeting the SIRT1/p53 signaling pathway during the pathogenesis of osteoarthritis.Int J Mol Med.2016;38(1):201209.
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[25]Fosang AJ,Last K,Kn?uper V,et al.Degradation of cartilage aggrecan by collagenase-3(MMP-13).FEBS Lett.1996;380(1-2):17-20.
[26]Goldring MB,Marcu KB.Cartilage homeostasis in health and rheumatic diseases.Arthritis ResTher.2009;11(3):224.
[27]Mitchell PG,Magna HA,Reeves LM,et al.Cloning,expression,and type II collagenolytic activity of matrix metalloproteinase-13 from human osteoarthritic cartilage.Clin Invest.1996;97(3):761-768.
[28]Wang M,Sampson ER,Jin H,et al.MMP13 is a critical target gene during the progression of osteoarthritis.Arthritis Res Ther.2013;15(1):R5.
[29]Loeser RF,Collins JA,Diekman BO.Ageing and the pathogenesis of osteoarthritis.Nat Rev Rheumatol.2016;12(7):412-20.
[30]Mobasheri A,Rayman MP,Gualillo O,et al.The role of metabolism in the pathogenesis of osteoarthritis.Nat Rev Rheumatol.2017;13(5):302-311.
[31]Kapoor M,Martel-Pelletier J,Lajeunesse D,et al.Role of proinflammatory cytokines in the pathophysiology of osteoarthritis.Nat Rev Rheumatol.2011;7(1):33-42.
[32]Tao L,Zeng Y,Wang J,et al.Differential microRNA expression in aristolochic acid-induced upper urothelial tract cancers ex vivo.Mol Med Rep.2015;12(5):6533-6546.
[33]Zhen Y,Xinghui Z,Chao W,et al.Several microRNAs could predict survival in patients with hepatitis B-related liver cancer.Sci Rep.2017;7:45195.
[34]Soyocak A,Kurt H,Ozgen M,et al.miRNA-146a,miRNA-155and JNK expression levels in peripheral blood mononuclear cells according to grade of knee osteoarthritis.Gene.2017;627:207-211.
[35]Tew SR,Mcdermott BT,Fentem RB,et al.Transcriptome-Wide Analysis of Messenger RNA Decay in Normal and Osteoarthritic Human Articular Chondrocytes.Arthritis Rheumatol.2015;66(11):3052-3061.
[36]Silvia DP,Claudia C,Emma ML,et al.Characterization of microRNA expression profiles in normal and osteoarthritic human chondrocytes.BMC Musculoskelet Disord.2012;13(1):144.
[37]Zhang Z,Kang Y,Zhang Z,et al.Expression of microRNAs during chondrogenesis of human adipose-derived stem cells.Osteoarthritis Cartilage.2012;20(12):1638-1646.
[38]Wang GL,Wu YB,Liu JT,et al.Upregulation of miR-98 inhibits apoptosis in cartilage cells in osteoarthriti.Genet Test Mol Biomarkers.2016;20(11):645-653.
[39]Zhang Y,Jie J,Yang S,et al.MicroRNA-21 controls the development of osteoarthritis by targeting GDF-5 in chondrocytes.Exp Mol Med.2014;46(2):e79.
[40]Zhang G,Sun Y,Wang Y,et al.MiR-502-5p inhibits IL-1?2-induced chondrocyte injury by targeting TRAF2.Cell Immunol.2016;302:50-57.
[41]Song J,Jin EH,Kim D,et al.MicroRNA-222 regulates MMP-13via targeting HDAC-4 during osteoarthritis pathogenesis.Bba Clinical.2015;3(1):79-89.
[42]Cao P,Feng Y,Deng M,et al.MiR-15b is a key regulator of proliferation and apoptosis of chondrocytes from patients with condylar hyperplasia by targeting IGF1,IGF1R and BCL2.Osteoarthritis Cartilage.2018.pii:S1063-4584(18)31481-X.
[43]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):1304-1316.
[44]Yang B,Ni J,Long H,et al.IL-1β-induced miR-34a up-regulation inhibits Cyr61 to modulate osteoarthritis chondrocyte proliferation through ADAMTS-4.J Cell Biochem.2018;119(10):7959-7970.
[45]Zhang W,Zhong B,Zhang C,et al.miR-373 regulates inflammatory cytokine-mediated chondrocyte proliferation in osteoarthritis by targeting the P2X7 receptor.FEBS Open Bio.2018;8(3):325-331.
[46]Wu J,Tao Y,Shang A,et al.Effect of the interaction between MiR-200b-3p and DNMT3A on cartilage cells of osteoarthritispatients.J Cell Mol Med.2017;21(10):2308-2316.
[47]He W,Cheng Y.Inhibition of miR-20 promotes proliferation and autophagy in articular chondrocytes by PI3K/AKT/mTORsignaling pathway.Biomed Pharmacother.2018;97:607-615.
[48]Shen PF,Qu YX,Wang B,et al.miR-30a-5p promotes the apoptosis of chondrocytes in patients with osteoarthritis by targeting protein kinase B.Zhonghua Yi Xue Za Zhi.2017;97(39):3079-3084.
[49]Chen L,Li Q,Wang J,et al.MiR-29b-3p promotes chondrocyte apoptosis and facilitates the occurrence and development of osteoarthritis by targeting PGRN.J Cell Mol Med.2017;21(12):3347-3359.
[50]Wang J,Chen L,Jin S,et al.MiR-98 promotes chondrocyte apoptosis by decreasing Bcl-2 expression in a rat model of osteoarthritis.Acta Biochim Biophys Sin(Shanghai).2016;48(10):923-929.
[51]Li X,He P,Li Z,et al.Interleukin 1βmediated suppression of microRNA 27a 3p activity in human cartilage via MAPK and NFκB pathways:A potential mechanism of osteoarthritis pathogenesis.Mol Med Rep.2018;18(1):541-549.
[52]Shi J,Guo K,Su S,et al.miR 486 5p is upregulated in osteoarthritis and inhibits chondrocyte proliferation and migration by suppressing SMAD2.Mol Med Rep.2018;18(1):502-508.
[53]Xu R,Li J,Wei B,et al.MicroRNA-483-5p Modulates the Expression of Cartilage-Related Genes in Human Chondrocytes through Down-Regulating TGF-β1Expression.Tohoku J Exp Med.2017;243(1):41-48.
[54]Wei ZJ,Liu J,Qin J.miR-138 suppressed the progression of osteoarthritis mainly through targeting p65.Eur Rev Med Pharmacol Sci.2017;21(9):2177-2184.
[55]Yin X,Wang JQ,Yan SY.Reduced miR 26a and miR 26b expression contributes to the pathogenesis of osteoarthritis via the promotion of p65 translocation.Mol Med Rep.2017;15(2):551-558.
[56]Mao G,Zhang Z,Huang Z,et al.MicroRNA-92a-3p regulates the expression of cartilage-specific genes by directly targeting histone deacetylase 2 in chondrogenesis and degradation.Osteoarthritis Cartilage.2017;25(4):521-532.
[57]Ji Q,Xu X,Xu Y,et al.miR-105/Runx2 axis mediates FGF2-induced ADAMTS expression in osteoarthritis cartilage.J Mol Med.2016;94(6):681-694.
[58]Ji Q,Xu X,Zhang Q,et al.The IL-1β/AP-1/miR-30a/ADAMTS-5axis regulates cartilage matrix degradation in human osteoarthritis.J Mol Med.2016;94(7):771-785.
[59]Wang G,Zhang Y,Zhao X,et al.MicroRNA-411 inhibited matrix metalloproteinase 13 expression in human chondrocytes.AmJTrans Res.2015;7(10):2000-2006.
[60]Zhang H,Song B,Pan Z.Downregulation of microRNA-9increases matrix metalloproteinase-13 expression levels and facilitates osteoarthritis onset.Mol Med Rep.2018;17(3):3708-3714.
[61]Kang L,Yang C,Song Y,et al.MicroRNA-23a-3p promotes the development of osteoarthritis by directly targeting SMAD3 in chondrocytes.Biochem Biophys Res Commun.2016;478(1):467-473.
[62]Ding Y,Wang L,Zhao Q,et al.MicroRNA 93 inhibits chondrocyte apoptosis and inflammation in osteoarthritis by targeting the TLR4/NF-κB signaling pathway.Int J Mol Med.2019;43:779-790.
[63]Wang X,Guo Y,Wang C,et al.MicroRNA-142-3p Inhibits Chondrocyte Apoptosis and Inflammation in Osteoarthritis by Targeting HMGB1.Inflammation.2016;39(5):1-11.
[64]Tardif G,Pelletier JP,Fahmi H,et al.NFAT3 and TGF-β/SMAD3regulate the expression of miR-140 in osteoarthritis.Arth Res Ther.2013;15(6):R197.
[65]Yang X,Guan Y,Tian S,et al.Mechanical and IL-1βResponsive miR-365 Contributes to Osteoarthritis Development by Targeting Histone Deacetylase 4.Int J Mol Sci.2016;17(4):436.
[66]Wang JH,Shih KS,Wu YW,et al.Histone deacetylase inhibitors increase microRNA-146a expression and enhance negative regulation of interleukin-1βsignaling in osteoarthritis fibroblast-like synoviocytes.Osteoarthritis Cartilage.2013;21(12):1987-1996.
[67]顾宗欣,王五洲.微小RNA对骨关节炎发生发展影响的研究进展[J].实用骨科杂志,2017,23(12):1102-1105.
[68]Cui X,Wang S,Cai H,et al.Overexpression of microRNA-634suppresses survival and matrix synthesis of human osteoarthritis chondrocytes by targeting PIK3R1.Sci Rep.2016;6:23117.
[69]Si HB,Zeng Y,Liu SY,et al.Intra-articular injection of microRNA-140(miRNA-140)alleviates osteoarthritis(OA)progression by modulating extracellular matrix(ECM)homeostasis in rats.Osteoarthritis Cartilage.2017;25(10):1698-1707.
[70]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;13:322-333.
[2]Fransen M,McConnell S,Harmer AR,et al.Exercise for osteoarthritis of the knee:A Cochrane systematic review.Br JSports Med.2015;49(24):1554-1557.
[3]Kopańska M,Szala D,Czech J,et al.MiRNA expression in the cartilage of patients with osteoarthritis.J Orthop Surg Res.2017;12(1):51.
[4]Aigner T,S?der S,Gebhard PM,et al.Mechanisms of Disease:role of chondrocytes in the pathogenesis of osteoarthritisstructure,chaos and senescence.Nat Clin Pract Rheumatol.2007;3(7):391-399.
[5]Le LT,Swingler TE,Clark IM.Review:the role of microRNAs in osteoarthritis and chondrogenesis.Arthritis Rheum.2013;65(8):1963-1974.
[6]Beyer C,Zampetaki A,Lin NY,et al.Signature of circulating microRNAs in osteoarthritis.Ann Rheum Dis.2015;74(3):e18.
[7]Cannell IG,Kong YW,Bushell M.How do microRNAs regulate gene expression?Biochem Soc Trans.2008;36:1224-1231.
[8]Ha M,Kim VN.Regulation of microRNA biogenesis.Nat Rev Mol Cell Biol.2014;15(8):509-524.
[9]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):843-854.
[10]Reinhart BJ,Slack FJ,Basson M.The 21-nucleotide let-7 RNAregulates developmental timing in Caenorhabditis elegans.Nature.2000;403(6772):901-906.
[11]Farh KK,Grimson A,Jan C,et al.The widespread impact of mammalian MicroRNAs on mRNA repression and evolution.Science.2005;310(5755):1817-1821.
[12]马圣运,白玉,韩凝,等.miRNA生物合成及其功能研究的新发现[J].遗传,2012,34(4):5-10.
[13]Carthew RW,Sontheimer EJ.Origins and mechanisms of miRNAs and siRNAs.Cell.2009;136(4):642-655.
[14]Zeng Y,Cullen BR.Structural requirements for premicroRNAbinding and nuclear export by Exportin 5.Nucleic Acids Res.2004;32(16):4776-4785.
[15]Rhoades MW,Reinhart BJ,Lim LP,et al.Prediction of plant microRNA targets.Cell.2002;110(4):513-520.
[16]Chen X.MicroRNA biogenesis and function in plants.FEBSLett.2005;579(26):5923-5931.
[17]Smalheiser NR,Torvik VI.Complications in mammalian microRNA target prediction.Methods Mol Biol.2006;342:115-127.
[18]Lewis BP,Shih IH,Jones-Rhoades MW,et al.Prediction of Mammalian MicroRNA Targets.Cell.2003;115(7):787-798.
[19]Yang M,Jiang L,Wang Q,et al.Traditional Chinese medicine for knee osteoarthritis:An overview of systematic review.Plos One.2017;12(12):e0189884.
[20]van der Kraan PM,van den Berg WB.Chondrocyte hypertrophy and osteoarthritis:role in initiation and progression of cartilage degeneration?Osteoarthritis Cartilage.2012;20(3):223-232.
[21]Nielsen FK,Egund N,J?rgensen A,et al.Risk factors for joint replacement in knee osteoarthritis;a 15-year follow-up study.BMC MusculoskeletDisord.2017;18(1):510.
[22]Duarte N,Rodrigues AM,Branco JDC,et al.Health and Lifestyles Factors Associated With Osteoarthritis among Older Adults in Portugal.Front Med(Lausanne).2017;4:192.
[23]Yan S,Wang M,Zhao J,et al.MicroRNA-34a affects chondrocyte apoptosis and proliferation by targeting the SIRT1/p53 signaling pathway during the pathogenesis of osteoarthritis.Int J Mol Med.2016;38(1):201209.
[24]Goldring MB.Update on the biology of the chondrocyte and new approaches to treating cartilage diseases.Best Pract Res Clin Rheumatol.2006;20(5):1003-1025.
[25]Fosang AJ,Last K,Kn?uper V,et al.Degradation of cartilage aggrecan by collagenase-3(MMP-13).FEBS Lett.1996;380(1-2):17-20.
[26]Goldring MB,Marcu KB.Cartilage homeostasis in health and rheumatic diseases.Arthritis ResTher.2009;11(3):224.
[27]Mitchell PG,Magna HA,Reeves LM,et al.Cloning,expression,and type II collagenolytic activity of matrix metalloproteinase-13 from human osteoarthritic cartilage.Clin Invest.1996;97(3):761-768.
[28]Wang M,Sampson ER,Jin H,et al.MMP13 is a critical target gene during the progression of osteoarthritis.Arthritis Res Ther.2013;15(1):R5.
[29]Loeser RF,Collins JA,Diekman BO.Ageing and the pathogenesis of osteoarthritis.Nat Rev Rheumatol.2016;12(7):412-20.
[30]Mobasheri A,Rayman MP,Gualillo O,et al.The role of metabolism in the pathogenesis of osteoarthritis.Nat Rev Rheumatol.2017;13(5):302-311.
[31]Kapoor M,Martel-Pelletier J,Lajeunesse D,et al.Role of proinflammatory cytokines in the pathophysiology of osteoarthritis.Nat Rev Rheumatol.2011;7(1):33-42.
[32]Tao L,Zeng Y,Wang J,et al.Differential microRNA expression in aristolochic acid-induced upper urothelial tract cancers ex vivo.Mol Med Rep.2015;12(5):6533-6546.
[33]Zhen Y,Xinghui Z,Chao W,et al.Several microRNAs could predict survival in patients with hepatitis B-related liver cancer.Sci Rep.2017;7:45195.
[34]Soyocak A,Kurt H,Ozgen M,et al.miRNA-146a,miRNA-155and JNK expression levels in peripheral blood mononuclear cells according to grade of knee osteoarthritis.Gene.2017;627:207-211.
[35]Tew SR,Mcdermott BT,Fentem RB,et al.Transcriptome-Wide Analysis of Messenger RNA Decay in Normal and Osteoarthritic Human Articular Chondrocytes.Arthritis Rheumatol.2015;66(11):3052-3061.
[36]Silvia DP,Claudia C,Emma ML,et al.Characterization of microRNA expression profiles in normal and osteoarthritic human chondrocytes.BMC Musculoskelet Disord.2012;13(1):144.
[37]Zhang Z,Kang Y,Zhang Z,et al.Expression of microRNAs during chondrogenesis of human adipose-derived stem cells.Osteoarthritis Cartilage.2012;20(12):1638-1646.
[38]Wang GL,Wu YB,Liu JT,et al.Upregulation of miR-98 inhibits apoptosis in cartilage cells in osteoarthriti.Genet Test Mol Biomarkers.2016;20(11):645-653.
[39]Zhang Y,Jie J,Yang S,et al.MicroRNA-21 controls the development of osteoarthritis by targeting GDF-5 in chondrocytes.Exp Mol Med.2014;46(2):e79.
[40]Zhang G,Sun Y,Wang Y,et al.MiR-502-5p inhibits IL-1?2-induced chondrocyte injury by targeting TRAF2.Cell Immunol.2016;302:50-57.
[41]Song J,Jin EH,Kim D,et al.MicroRNA-222 regulates MMP-13via targeting HDAC-4 during osteoarthritis pathogenesis.Bba Clinical.2015;3(1):79-89.
[42]Cao P,Feng Y,Deng M,et al.MiR-15b is a key regulator of proliferation and apoptosis of chondrocytes from patients with condylar hyperplasia by targeting IGF1,IGF1R and BCL2.Osteoarthritis Cartilage.2018.pii:S1063-4584(18)31481-X.
[43]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):1304-1316.
[44]Yang B,Ni J,Long H,et al.IL-1β-induced miR-34a up-regulation inhibits Cyr61 to modulate osteoarthritis chondrocyte proliferation through ADAMTS-4.J Cell Biochem.2018;119(10):7959-7970.
[45]Zhang W,Zhong B,Zhang C,et al.miR-373 regulates inflammatory cytokine-mediated chondrocyte proliferation in osteoarthritis by targeting the P2X7 receptor.FEBS Open Bio.2018;8(3):325-331.
[46]Wu J,Tao Y,Shang A,et al.Effect of the interaction between MiR-200b-3p and DNMT3A on cartilage cells of osteoarthritispatients.J Cell Mol Med.2017;21(10):2308-2316.
[47]He W,Cheng Y.Inhibition of miR-20 promotes proliferation and autophagy in articular chondrocytes by PI3K/AKT/mTORsignaling pathway.Biomed Pharmacother.2018;97:607-615.
[48]Shen PF,Qu YX,Wang B,et al.miR-30a-5p promotes the apoptosis of chondrocytes in patients with osteoarthritis by targeting protein kinase B.Zhonghua Yi Xue Za Zhi.2017;97(39):3079-3084.
[49]Chen L,Li Q,Wang J,et al.MiR-29b-3p promotes chondrocyte apoptosis and facilitates the occurrence and development of osteoarthritis by targeting PGRN.J Cell Mol Med.2017;21(12):3347-3359.
[50]Wang J,Chen L,Jin S,et al.MiR-98 promotes chondrocyte apoptosis by decreasing Bcl-2 expression in a rat model of osteoarthritis.Acta Biochim Biophys Sin(Shanghai).2016;48(10):923-929.
[51]Li X,He P,Li Z,et al.Interleukin 1βmediated suppression of microRNA 27a 3p activity in human cartilage via MAPK and NFκB pathways:A potential mechanism of osteoarthritis pathogenesis.Mol Med Rep.2018;18(1):541-549.
[52]Shi J,Guo K,Su S,et al.miR 486 5p is upregulated in osteoarthritis and inhibits chondrocyte proliferation and migration by suppressing SMAD2.Mol Med Rep.2018;18(1):502-508.
[53]Xu R,Li J,Wei B,et al.MicroRNA-483-5p Modulates the Expression of Cartilage-Related Genes in Human Chondrocytes through Down-Regulating TGF-β1Expression.Tohoku J Exp Med.2017;243(1):41-48.
[54]Wei ZJ,Liu J,Qin J.miR-138 suppressed the progression of osteoarthritis mainly through targeting p65.Eur Rev Med Pharmacol Sci.2017;21(9):2177-2184.
[55]Yin X,Wang JQ,Yan SY.Reduced miR 26a and miR 26b expression contributes to the pathogenesis of osteoarthritis via the promotion of p65 translocation.Mol Med Rep.2017;15(2):551-558.
[56]Mao G,Zhang Z,Huang Z,et al.MicroRNA-92a-3p regulates the expression of cartilage-specific genes by directly targeting histone deacetylase 2 in chondrogenesis and degradation.Osteoarthritis Cartilage.2017;25(4):521-532.
[57]Ji Q,Xu X,Xu Y,et al.miR-105/Runx2 axis mediates FGF2-induced ADAMTS expression in osteoarthritis cartilage.J Mol Med.2016;94(6):681-694.
[58]Ji Q,Xu X,Zhang Q,et al.The IL-1β/AP-1/miR-30a/ADAMTS-5axis regulates cartilage matrix degradation in human osteoarthritis.J Mol Med.2016;94(7):771-785.
[59]Wang G,Zhang Y,Zhao X,et al.MicroRNA-411 inhibited matrix metalloproteinase 13 expression in human chondrocytes.AmJTrans Res.2015;7(10):2000-2006.
[60]Zhang H,Song B,Pan Z.Downregulation of microRNA-9increases matrix metalloproteinase-13 expression levels and facilitates osteoarthritis onset.Mol Med Rep.2018;17(3):3708-3714.
[61]Kang L,Yang C,Song Y,et al.MicroRNA-23a-3p promotes the development of osteoarthritis by directly targeting SMAD3 in chondrocytes.Biochem Biophys Res Commun.2016;478(1):467-473.
[62]Ding Y,Wang L,Zhao Q,et al.MicroRNA 93 inhibits chondrocyte apoptosis and inflammation in osteoarthritis by targeting the TLR4/NF-κB signaling pathway.Int J Mol Med.2019;43:779-790.
[63]Wang X,Guo Y,Wang C,et al.MicroRNA-142-3p Inhibits Chondrocyte Apoptosis and Inflammation in Osteoarthritis by Targeting HMGB1.Inflammation.2016;39(5):1-11.
[64]Tardif G,Pelletier JP,Fahmi H,et al.NFAT3 and TGF-β/SMAD3regulate the expression of miR-140 in osteoarthritis.Arth Res Ther.2013;15(6):R197.
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