Role of MicroRNA in Osteoarthritis

Mingcai Zhang, Kate Lygrisse, Jinxi Wang, Mingcai Zhang, Kate Lygrisse, Jinxi Wang

Abstract

Although the potential effect of aberrant expression of catabolic and anabolic genes on the development of osteoarthritis (OA) is well-documented, the regulatory mechanism for the expression of these genes in articular chondrocytes remains to be elucidated. The recent advances in epigenetic studies have identified microRNA (miRNA) as one of the epigenetic mechanisms for the regulation of gene expression. This mini review highlights the role of miRNA in the regulation of gene expression in articular chondrocytes and its significance in the pathogenesis of OA, with a discussion on the potential of miRNA as a new biomarker and therapeutic target for OA. Further investigations are required to determine the specificity, sensitivity, and efficacy of miRNA for clinical applications.

Keywords: Biomarker; Epigenetics; Gene expression; MicroRNA; Osteoarthritis.

Conflict of interest statement

Conflicts of interest The authors declare no conflicts of interest

References

    1. Saetrom P, Snove O, Jr, Rossi JJ. Epigenetics and microRNAs. Pediatr Res. 2007;61:17r–23r.
    1. Dawson MA, Kouzarides T. Cancer epigenetics: from mechanism to therapy. Cell. 2012;150:12–27.
    1. Murphy L, Helmick CG. The impact of osteoarthritis in the United States: a population-health perspective. Am J Nurs. 2012;112:S13–S19.
    1. Mattick JS, Makunin IV. Non-coding RNA. Hum Mol Genet. 2006;15(Spec No 1):R17–R29.
    1. Ha M, Kim VN. Regulation of microRNA biogenesis. Nature reviews Molecular cell biology. 2014;8:509–524.
    1. Tortorella MD, Malfait AM, Deccico C, Arner E. The role of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) in a model of cartilage degradation. Osteoarthritis and cartilage/OARS, Osteoarthritis Research Society. 2001;9:539–552.
    1. Glasson SS, Askew R, Sheppard B, Carito B, Blanchet T, et al. Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis. Nature. 2005;434:644–648.
    1. Stanton H, Rogerson FM, East CJ, Golub SB, Lawlor KE, et al. ADAMTS5 is the major aggrecanase in mouse cartilage in vivo and in vitro. Nature. 2005;434:648–652.
    1. Rogerson FM, Stanton H, East CJ, Golub SB, Tutolo L, et al. Evidence of a novel aggrecan-degrading activity in cartilage: Studies of mice deficient in both ADAMTS-4 and ADAMTS-5. Arthritis and rheumatism. 2008;58:1664–1673.
    1. Little CB, Barai A, Burkhardt D, Smith SM, Fosang AJ, et al. Matrix metalloproteinase 13-deficient mice are resistant to osteoarthritic cartilage erosion but not chondrocyte hypertrophy or osteophyte development. Arthritis and rheumatism. 2009;60:3723–3733.
    1. Neuhold LA, Killar L, Zhao W, Sung ML, Warner L, et al. Postnatal expression in hyaline cartilage of constitutively active human collagenase-3 (MMP-13) induces osteoarthritis in mice. J Clin Invest. 2001;107:35–44.
    1. Goldring MB. Osteoarthritis and cartilage: the role of cytokines. Curr Rheumatol Rep. 2000;2:459–465.
    1. Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H, et al. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nature reviews Rheumatology. 2011;7:33–42.
    1. Kamekura S, Kawasaki Y, Hoshi K, Shimoaka T, Chikuda H, et al. Contribution of runt-related transcription factor 2 to the pathogenesis of osteoarthritis in mice after induction of knee joint instability. Arthritis and rheumatism. 2006;54:2462–2470.
    1. Malfait AM, Liu RQ, Ijiri K, Komiya S, Tortorella MD. Inhibition of ADAM-TS4 and ADAM-TS5 prevents aggrecan degradation in osteoarthritic cartilage. The Journal of biological chemistry. 2002;277:22201–22208.
    1. Song RH, Tortorella MD, Malfait AM, Alston JT, Yang Z, et al. Aggrecan degradation in human articular cartilage explants is mediated by both ADAMTS-4 and ADAMTS-5. Arthritis and rheumatism. 2007;56:575–585.
    1. Eid K, Thornhill TS, Glowacki J. Chondrocyte gene expression in osteoarthritis: Correlation with disease severity. Journal of orthopaedic research: official publication of the Orthopaedic Research Society. 2006;24:1062–1068.
    1. Chambers MG, Kuffner T, Cowan SK, Cheah KS, Mason RM, et al. Expression of collagen and aggrecan genes in normal and osteoarthritic murine knee joints. Osteoarthritis and cartilage/OARS, Osteoarthritis Research Society. 2002;10:51–61.
    1. Saamanen AK, Salminen HJ, Dean PB, De Crombrugghe B, Vuorio EI, et al. Osteoarthritis-like lesions in transgenic mice harboring a small deletion mutation in type II collagen gene. Osteoarthritis and cartilage/OARS, Osteoarthritis Research Society. 2000;8:248–257.
    1. Lefebvre V, Li P, de Crombrugghe B. A new long form of Sox5 (L-Sox5), Sox6 and Sox9 are coexpressed in chondrogenesis and cooperatively activate the type II collagen gene. Embo j. 1998;17:5718–5733.
    1. Bi W, Deng JM, Zhang Z, Behringer RR, de Crombrugghe B. Sox9 is required for cartilage formation. Nat Genet. 1999;22:85–89.
    1. Henry SP, Liang S, Akdemir KC, de Crombrugghe B. The postnatal role of Sox9 in cartilage. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research. 2012;27:2511–2525.
    1. Lee JS, Im GI. SOX trio decrease in the articular cartilage with the advancement of osteoarthritis. Connect Tissue Res. 2011;52:496–502.
    1. Hodge MR, Ranger AM, Charles de la Brousse F, Hoey T, Grusby MJ, et al. Hyperproliferation and dysregulation of IL-4 expression in NF-ATp-deficient mice. Immunity. 1996;4:397–405.
    1. Xanthoudakis S, Viola JP, Shaw KT, Luo C, Wallace JD, et al. An enhanced immune response in mice lacking the transcription factor NFAT1. Science. 1996;272:892–895.
    1. Wang J, Gardner BM, Lu Q, Rodova M, Woodbury BG, et al. Transcription factor Nfat1 deficiency causes osteoarthritis through dysfunction of adult articular chondrocytes. J Pathol. 2009;219:163–172.
    1. Rodova M, Lu Q, Li Y, Woodbury BG, Crist JD, et al. Nfat1 regulates adult articular chondrocyte function through its age-dependent expression mediated by epigenetic histone methylation. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research. 2011;26:1974–1986.
    1. Zhang M, Egan B, Wang J. Epigenetic mechanisms underlying the aberrant catabolic and anabolic activities of osteoarthritic chondrocytes. The international journal of biochemistry & cell biology. 2015;67:101–109.
    1. Zhang M, Lu Q, Egan B, Zhong XB, Brandt K, et al. Epigenetically mediated spontaneous reduction of NFAT1 expression causes imbalanced metabolic activities of articular chondrocytes in aged mice. Osteoarthritis and cartilage. 2016;24:1274–1283.
    1. Meng F, Zhang Z, Chen W, Huang G, He A, et al. MicroRNA-320 regulates matrix metalloproteinase-13 expression in chondrogenesis and interleukin-1beta-induced chondrocyte responses. Osteoarthritis and cartilage/OARS, Osteoarthritis Research Society. 2016;24:932–941.
    1. Lu X, Lin J, Jin J, Qian W, Weng X. Hsa-miR-15a exerts protective effects against osteoarthritis by targeting aggrecanase-2 (ADAMTS5) in human chondrocytes. International journal of molecular medicine. 2016;37:509–516.
    1. Wang G, Zhang Y, Zhao X, Meng C, Ma L, et al. MicroRNA-411 inhibited matrix metalloproteinase 13 expression in human chondrocytes. American journal of translational research. 2015;7:2000–2006.
    1. Gu R, Liu N, Luo S, Huang W, Zha Z, et al. MicroRNA-9 regulates the development of knee osteoarthritis through the NF-kappaB1 pathway in chondrocytes. Medicine. 2016;95:e4315.
    1. Zhang D, Cao X, Li J, Zhao G. MiR-210 inhibits NF-kappaB signaling pathway by targeting DR6 in osteoarthritis. Scientific reports. 2015;5:12775.
    1. Cheleschi S, De Palma A, Pecorelli A, Pascarelli NA, Valacchi G, et al. Hydrostatic Pressure Regulates MicroRNA Expression Levels in Osteoarthritic Chondrocyte Cultures via the Wnt/beta-Catenin Pathway. International journal of molecular sciences. 2017:18.
    1. Yan S, Wang M, Zhao J, Zhang H, Zhou C, et al. MicroRNA-34a affects chondrocyte apoptosis and proliferation by targeting the SIRT1/p53 signaling pathway during the pathogenesis of osteoarthritis. International journal of molecular medicine. 2016;38:201–209.
    1. Zheng X, Zhao FC, Pang Y, Li DY, Yao SC, et al. Downregulation of miR-221-3p contributes to IL-1beta-induced cartilage degradation by directly targeting the SDF1/CXCR4 signaling pathway. Journal of molecular medicine 2017
    1. Martinez-Sanchez A, Dudek KA, Murphy CL. Regulation of human chondrocyte function through direct inhibition of cartilage master regulator SOX9 by microRNA-145 (miRNA-145) The Journal of biological chemistry. 2012;287:916–924.
    1. Chang T, Xie J, Li H, Li D, Liu P, et al. MicroRNA-30a promotes extracellular matrix degradation in articular cartilage via downregulation of Sox9. Cell proliferation. 2016;49:207–218.
    1. Mao G, Zhang Z, Huang Z, Chen W, Huang G, et al. MicroRNA-92a-3p regulates the expression of cartilage-specific genes by directly targeting histone deacetylase 2 in chondrogenesis and degradation. Osteoarthritis and cartilage/OARS, Osteoarthritis Research Society 2016
    1. Chen W, Sheng P, Huang Z, Meng F, Kang Y, et al. MicroRNA-381 Regulates Chondrocyte Hypertrophy by Inhibiting Histone Deacetylase 4 Expression. International journal of molecular sciences. 2016:17.
    1. Song J, Jin EH, Kim D, Kim KY, Chun CH, et al. MicroRNA-222 regulates MMP-13 via targeting HDAC-4 during osteoarthritis pathogenesis. BBA clinical. 2015;3:79–89.
    1. Yang X, Guan Y, Tian S, Wang Y, Sun K, et al. Mechanical and IL-1beta Responsive miR-365 contributes to Osteoarthritis Development by Targeting Histone Deacetylase 4. International journal of molecular sciences. 2016;17:436.
    1. Park KW, Lee KM, Yoon DS, Park KH, Choi WJ, et al. Inhibition of microRNA-449a prevents IL-1beta-induced cartilage destruction via SIRT1. Osteoarthritis and cartilage/OARS, Osteoarthritis Research Society. 2016;24:2153–2161.
    1. Chevalier X, Goupille P, Beaulieu AD, Burch FX, Bensen WG, et al. Intraarticular injection of anakinra in osteoarthritis of the knee: a multicenter, randomized, double-blind, placebo-controlled study. Arthritis and rheumatism. 2009;61:344–352.
    1. Hellio le Graverand MP, Clemmer RS, Redifer P, Brunell RM, Hayes CW, et al. A 2-year randomised, double-blind, placebo-controlled, multicentre study of oral selective iNOS inhibitor, cindunistat (SD-6010), in patients with symptomatic osteoarthritis of the knee. Annals of the rheumatic diseases. 2013;72:187–195.
    1. Hellio Le Graverand-Gastineau MP. OA clinical trials: current targets and trials for OA. Choosing molecular targets: what have we learned and where we are headed? Osteoarthritis and cartilage/OARS, Osteoarthritis Research Society. 2009;17:1393–1401.
    1. Shi J, Wei Y, Xia J, Wang S, Wu J, et al. MicroRNAs are potential prognostic and therapeutic targets in diabetic osteoarthritis. J Bone Miner Metab. 2015;33:1–8.
    1. Wang H, Zhang H, Sun Q, Wang Y, Yang J, et al. Intra-articular Delivery of Antago-miR 483-5p Inhibits Osteoarthritis by Modulating Matrilin 3 and Tissue Inhibitor of Metalloproteinase 2. Molecular therapy: the journal of the American Society of Gene Therapy. 2017;25:715–727.
    1. Li YH, Tavallaee G, Tokar T, Nakamura A, Sundararajan K, et al. Identification of synovial fluid microRNA signature in knee osteoarthritis: differentiating early- and late-stage knee osteoarthritis. Osteoarthritis and cartilage/OARS, Osteoarthritis Research Society. 2016;24:1577–1586.
    1. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proceedings of the National Academy of Sciences of the United States of America. 2008;105:10513–10518.
    1. Beyer C, Zampetaki A, Lin NY, Kleyer A, Perricone C, et al. Signature of circulating microRNAs in osteoarthritis. Annals of the rheumatic diseases. 2015;74:e18.
    1. Bernard NJ. Osteoarthritis: circulating miRNAs-early osteoarthritis biomarkers? Nature reviews Rheumatology. 2014;10:197.
    1. Matsukawa T, Sakai T, Yonezawa T, Hiraiwa H, Hamada T, et al. MicroRNA-125b regulates the expression of aggrecanase-1 (ADAMTS-4) in human osteoarthritic chondrocytes. Arthritis research & therapy. 2013;15:R28.
    1. Miyaki S, Sato T, Inoue A, Otsuki S, Ito Y, et al. MicroRNA-140 plays dual roles in both cartilage development and homeostasis. Genes & development. 2010;24:1173–1185.
    1. Ji Q, Xu X, Zhang Q, Kang L, Xu Y, et al. The IL-1beta/AP-1/miR-30a/ADAMTS-5 axis regulates cartilage matrix degradation in human osteoarthritis. Journal of molecular medicine (Berlin, Germany) 2016;94:771–785.
    1. Wang J, Chen L, Jin S, Lin J, Zheng H, et al. MiR-98 promotes chondrocyte apoptosis by decreasing Bcl-2 expression in a rat model of osteoarthritis. Acta biochimica et biophysica Sinica. 2016;48:923–929.
    1. Akhtar N, Haqqi TM. MicroRNA-199a regulates the expression of cyclooxygenase-2 in human chondrocytes. Annals of the rheumatic diseases. 2012;71:1073–1080.
    1. Xu J, Liu Y, Deng M, Li J, Cai H, et al. MicroRNA221-3p modulates Ets-1 expression in synovial fibroblasts from patients with osteoarthritis of temporomandibular joint. Osteoarthritis and cartilage/OARS, Osteoarthritis Research Society. 2016;24:2003–2011.
    1. Yuan Y, Zhang GQ, Chai W, Ni M, Xu C, et al. Silencing of microRNA-138-5p promotes IL-1beta-induced cartilage degradation in human chondrocytes by targeting FOXC1: miR-138 promotes cartilage degradation. Bone & joint research. 2016;5:523–530.
    1. Zhang Y, Jia J, Yang S, Liu X, Ye S, et al. MicroRNA-21 controls the development of osteoarthritis by targeting GDF-5 in chondrocytes. Experimental & molecular medicine. 2014;46:e79.
    1. Mao G, Zhang Z, Huang Z, Chen W, Huang G, et al. MicroRNA-92a-3p regulates the expression of cartilage-specific genes by directly targeting histone deacetylase 2 in chondrogenesis and degradation. Osteoarthritis and cartilage/OARS, Osteoarthritis Research Society. 2017;25:521–532.
    1. Wang X, Guo Y, Wang C, Yu H, Yu X, et al. MicroRNA-142-3p Inhibits Chondrocyte Apoptosis and Inflammation in Osteoarthritis by Targeting HMGB1. 2016;39:1718–1728.
    1. Tardif G, Hum D, Pelletier JP, Duval N, Martel-Pelletier J, et al. Regulation of the IGFBP-5 and MMP-13 genes by the microRNAs miR-140 and miR-27a in human osteoarthritic chondrocytes. BMC musculoskeletal disorders. 2009;10:148.
    1. Xia S, Yan K, Wang Y. Increased miR-381a-3p Contributes to Osteoarthritis by Targeting IkBalpha. Annals of clinical and laboratory science. 2016;46:247–253.
    1. Rasheed Z, Al-Shobaili HA, Rasheed N, Mahmood A, Khan MI, et al. MicroRNA-26a-5p regulates the expression of inducible nitric oxide synthase via activation of NF-kappaB pathway in human osteoarthritis chondrocytes. Archives of biochemistry and biophysics. 2016;594:61–67.
    1. Makki MS, Haqqi TM. miR-139 modulates MCPIP1/IL-6 expression and induces apoptosis in human OA chondrocytes. Experimental & molecular medicine. 2015;47:e189.
    1. Song J, Kim D, Chun CH, Jin EJ. miR-370 and miR-373 regulate the pathogenesis of osteoarthritis by modulating onecarbon metabolism via SHMT-2 and MECP-2, respectively. Aging cell. 2015;14:826–837.
    1. Akhtar N, Rasheed Z, Ramamurthy S, Anbazhagan AN, Voss FR, et al. MicroRNA-27b regulates the expression of matrix metalloproteinase 13 in human osteoarthritis chondrocytes. Arthritis and rheumatism. 2010;62:1361–1371.
    1. Park SJ, Cheon EJ, Lee MH, Kim HA. MicroRNA-127-5p regulates matrix metalloproteinase 13 expression and interleukin-1beta-induced catabolic effects in human chondrocytes. Arthritis and rheumatism. 2013;65:3141–3152.
    1. Cui X, Wang S, Cai H, Lin Y, Zheng X, et al. Overexpression of microRNA-634 suppresses survival and matrix synthesis of human osteoarthritis chondrocytes by targeting PIK3R1. Scientific reports. 2016;6:23117.
    1. Yang B, Kang X, Xing Y, Dou C, Kang F, et al. Effect of microRNA-145 on IL-1beta-induced cartilage degradation in human chondrocytes. FEBS letters. 2014;588:2344–2352.
    1. Li J, Huang J, Dai L, Yu D, Chen Q, et al. miR-146a, an IL-1beta responsive miRNA, induces vascular endothelial growth factor and chondrocyte apoptosis by targeting Smad4. Arthritis research & therapy. 2012;14:R75.
    1. Dai L, Zhang X, Hu X, Zhou C, Ao Y. Silencing of microRNA-101 prevents IL-1beta-induced extracellular matrix degradation in chondrocytes. Arthritis research & therapy. 2012;14:R268.
    1. Ge FX, Li H, Yin X. Upregulation of microRNA-125b-5p is involved in the pathogenesis of osteoarthritis by downregulating SYVN1. Oncology reports. 2017;37:2490–2496.
    1. Li ZC, Han N, Li X, Li G, Liu YZ, et al. Decreased expression of microRNA-130a correlates with TNF-alpha in the development of osteoarthritis. International journal of clinical and experimental pathology. 2015;8:2555–2564.
    1. Wang GD, Zhao XW, Zhang YG, Kong Y, Niu SS, et al. Effects of miR-145 on the inhibition of chondrocyte proliferation and fibrosis by targeting TNFRSF11B in human osteoarthritis. Molecular medicine reports. 2017;15:75–80.
    1. Zhang G, Sun Y, Wang Y, Liu R, Bao Y, et al. MiR-502-5p inhibits IL-1beta-induced chondrocyte injury by targeting TRAF2. Cellular immunology. 2016;302:50–57.

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