Skip to main content

Advertisement

Log in

The Role of MicroRNAs and Their Targets in Osteoarthritis

  • Osteoarthritis (MB Goldring, Section Editor)
  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Micro ribonucleic acid (microRNA) regulation and expression has become an emerging field in determining the mechanisms regulating a variety of inflammation-mediated diseases. Several studies have focused on specific microRNAs that are differentially expressed in cases of osteoarthritis. Furthermore, several targets of these miRNAs important in disease progression have also been identified. In this review, we focus on microRNA biogenesis, regulation, detection, and quantification with an emphasis on cellular localization and how these concepts may be linked to disease processes such as osteoarthritis. Next, we review the relationships of specific microRNAs to certain features and risk factors associated with osteoarthritis such as inflammation, obesity, autophagy, and cartilage homeostasis. We also identify certain microRNAs that are differentially expressed in osteoarthritis but have unidentified targets and functions in the disease state. Lastly, we identify the potential use of microRNAs for therapeutic purposes and also mention certain remedies that regulate microRNA expression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Vennu V, Bindawas SM. Relationship between falls, knee osteoarthritis, and health-related quality of life: data from the Osteoarthritis Initiative study. Clin Interv Aging. 2014;9:793–800.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75:843–54.

    Article  CAS  PubMed  Google Scholar 

  3. Abente EJ, Subramanian M, Ramachandran V, Najafi-Shoushtari SH. MicroRNAs in obesity-associated disorders. Arch Biochem Biophys. 2016;589:108–19.

    Article  CAS  PubMed  Google Scholar 

  4. Small EM, Olson EN. Pervasive roles of microRNAs in cardiovascular biology. Nature. 2011;469:336–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103:2257–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Yu XM, Meng HY, Yuan XL, Wang Y, Guo QY, Peng J, et al. MicroRNAs’ involvement in osteoarthritis and the prospects for treatments. Evid Based Complement Alternat Med. 2015;2015:236179.

    PubMed  PubMed Central  Google Scholar 

  7. Nugent M. MicroRNAs: exploring new horizons in osteoarthritis. Osteoarthr Cartil. 2016;24:573–80.

    Article  CAS  PubMed  Google Scholar 

  8. Marques-Rocha JL, Samblas M, Milagro FI, Bressan J, Martinez JA, Marti A. Noncoding RNAs, cytokines, and inflammation-related diseases. FASEB J. 2015;29:3595–611. This review highlights the role of noncoding RNAs in the transcriptional regulation of inflammatory mediators in a variety of disease processes.

    Article  CAS  PubMed  Google Scholar 

  9. Ibanez-Ventoso C, Vora M, Driscoll M. Sequence relationships among C. elegans, D. melanogaster and human microRNAs highlight the extensive conservation of microRNAs in biology. PLoS One. 2008;3:e2818.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Kim VN, Han J, Siomi MC. Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol. 2009;10:126–39.

    Article  CAS  PubMed  Google Scholar 

  11. Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, et al. MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 2004;23:4051–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cai X, Hagedorn CH, Cullen BR. Human microRNAs are processed from capped, polyadenylated transcripts that can also function as mRNAs. RNA. 2004;10:1957–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Borchert GM, Lanier W, Davidson BL. RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol. 2006;13:1097–101.

    Article  CAS  PubMed  Google Scholar 

  14. Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, et al. The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003;425:415–9.

    Article  CAS  PubMed  Google Scholar 

  15. Han J, Lee Y, Yeom KH, Kim YK, Jin H, Kim VN. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 2004;18:3016–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lund E, Guttinger S, Calado A, Dahlberg JE, Kutay U. Nuclear export of microRNA precursors. Science. 2004;303:95–8.

    Article  CAS  PubMed  Google Scholar 

  17. Bernstein E, Caudy AA, Hammond SM, Hannon GJ. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001;409:363–6.

    Article  CAS  PubMed  Google Scholar 

  18. Grishok A, Pasquinelli AE, Conte D, Li N, Parrish S, Ha I, et al. Genes and mechanisms related to RNA interference regulate expression of the small temporal RNAs that control C. elegans developmental timing. Cell. 2001;106:23–34.

    Article  CAS  PubMed  Google Scholar 

  19. Hutvagner G, McLachlan J, Pasquinelli AE, Balint E, Tuschl T, Zamore PD. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science. 2001;293:834–8.

    Article  CAS  PubMed  Google Scholar 

  20. Hammond SM, Boettcher S, Caudy AA, Kobayashi R, Hannon GJ. Argonaute2, a link between genetic and biochemical analyses of RNAi. Science. 2001;293:1146–50.

    Article  CAS  PubMed  Google Scholar 

  21. Ha M, Kim VN. Regulation of microRNA biogenesis. Nat Rev Mol Cell Biol. 2014;15:509–24. This review focuses on the mechanisms involved in miRNA development. It highlights several aspects of miRNA biogenesis including regulation and modification, and briefly describes recently discovered non-canonical pathways for miRNA biogenesis.

    Article  CAS  PubMed  Google Scholar 

  22. Leung AK. The whereabouts of microRNA actions: cytoplasm and beyond. Trends Cell Biol. 2015;25:601–10. This article discusses the localization of miRNAs and their associated regulatory machinery to different subcellular compartments. Furthermore, the authors discuss the potential physiological relevance of location-specific miRNAs.

    Article  CAS  PubMed  Google Scholar 

  23. Turchinovich A, Burwinkel B. Distinct AGO1 and AGO2 associated miRNA profiles in human cells and blood plasma. RNA Biol. 2012;9:1066–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Turchinovich A, Samatov TR, Tonevitsky AG, Burwinkel B. Circulating miRNAs: cell-cell communication function? Front Genet. 2013;4:119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Winter J, Diederichs S. Argonaute proteins regulate microRNA stability: increased microRNA abundance by Argonaute proteins is due to microRNA stabilization. RNA Biol. 2011;8:1149–57.

    Article  CAS  PubMed  Google Scholar 

  26. Yu Z, Hecht NB. The DNA/RNA-binding protein, translin, binds microRNA122a and increases its in vivo stability. J Androl. 2008;29:572–9.

    Article  CAS  PubMed  Google Scholar 

  27. King IN, Yartseva V, Salas D, Kumar A, Heidersbach A, Ando DM, et al. The RNA-binding protein TDP-43 selectively disrupts microRNA-1/206 incorporation into the RNA-induced silencing complex. J Biol Chem. 2014;289:14263–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Eiring AM, Harb JG, Neviani P, Garton C, Oaks JJ, Spizzo R, et al. miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blasts. Cell. 2010;140:652–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Eulalio A, Behm-Ansmant I, Izaurralde E. P bodies: at the crossroads of post-transcriptional pathways. Nat Rev Mol Cell Biol. 2007;8:9–22.

    Article  CAS  PubMed  Google Scholar 

  30. Liu J, Valencia-Sanchez MA, Hannon GJ, Parker R. MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies. Nat Cell Biol. 2005;7:719–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kim YJ, Maizel A, Chen X. Traffic into silence: endomembranes and post-transcriptional RNA silencing. EMBO J. 2014;33:968–80. This review describes the role of cellular endomembrane compartments in RNA gene silencing.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Stalder L, Heusermann W, Sokol L, Trojer D, Wirz J, Hean J, et al. The rough endoplasmatic reticulum is a central nucleation site of siRNA-mediated RNA silencing. EMBO J. 2013;32:1115–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Lee YS, Pressman S, Andress AP, Kim K, White JL, Cassidy JJ, et al. Silencing by small RNAs is linked to endosomal trafficking. Nat Cell Biol. 2009;11:1150–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Gibbings DJ, Ciaudo C, Erhardt M, Voinnet O. Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity. Nat Cell Biol. 2009;11:1143–9.

    Article  CAS  PubMed  Google Scholar 

  35. Kohlhapp FJ, Mitra AK, Lengyel E, Peter ME. MicroRNAs as mediators and communicators between cancer cells and the tumor microenvironment. Oncogene. 2015;34:5857–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MA, Hopmans ES, Lindenberg JL, et al. Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci U S A. 2010;107:6328–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zomer A, Vendrig T, Hopmans ES, van Eijndhoven M, Middeldorp JM, Pegtel DM. Exosomes: fit to deliver small RNA. Commun Integr Biol. 2010;3:447–50.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Hwang HW, Wentzel EA, Mendell JT. A hexanucleotide element directs microRNA nuclear import. Science. 2007;315:97–100.

    Article  CAS  PubMed  Google Scholar 

  39. Park CW, Zeng Y, Zhang X, Subramanian S, Steer CJ. Mature microRNAs identified in highly purified nuclei from HCT116 colon cancer cells. RNA Biol. 2010;7:606–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Gagnon KT, Li L, Chu Y, Janowski BA, Corey DR. RNAi factors are present and active in human cell nuclei. Cell Rep. 2014;6:211–21. This manuscript investigates the role of RNAi components in cell nuclei, and describe distinguishing features between nuclear and cytoplasmic RNA processing.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Politz JC, Zhang F, Pederson T. MicroRNA-206 colocalizes with ribosome-rich regions in both the nucleolus and cytoplasm of rat myogenic cells. Proc Natl Acad Sci U S A. 2006;103:18957–62.

    Article  CAS  PubMed  Google Scholar 

  42. Roberts TC. The microRNA biology of the mammalian nucleus. Mol Ther Nucleic Acids. 2014;3:e188.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Saldanha G, Potter L, Lee YS, Watson S, Shendge P, Pringle JH. MicroRNA-21 expression and its pathogenetic significance in cutaneous melanoma. Melanoma Res. 2016;26:21–8.

    Article  CAS  PubMed  Google Scholar 

  44. Boulon S, Westman BJ, Hutten S, Boisvert FM, Lamond AI. The nucleolus under stress. Mol Cell. 2010;40:216–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Li ZF, Liang YM, Lau PN, Shen W, Wang DK, Cheung WT, et al. Dynamic localisation of mature microRNAs in human nucleoli is influenced by exogenous genetic materials. PLoS One. 2013;8:e70869.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Bai B, Liu H, Laiho M. Small RNA expression and deep sequencing analyses of the nucleolus reveal the presence of nucleolus-associated microRNAs. FEBS Open Bio. 2014;4:441–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Castanotto D, Lingeman R, Riggs AD, Rossi JJ. CRM1 mediates nuclear-cytoplasmic shuttling of mature microRNAs. Proc Natl Acad Sci U S A. 2009;106:21655–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Lung B, Zemann A, Madej MJ, Schuelke M, Techritz S, Ruf S, et al. Identification of small non-coding RNAs from mitochondria and chloroplasts. Nucleic Acids Res. 2006;34:3842–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kren BT, Wong PY, Sarver A, Zhang X, Zeng Y, Steer CJ. MicroRNAs identified in highly purified liver-derived mitochondria may play a role in apoptosis. RNA Biol. 2009;6:65–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Bian Z, Li LM, Tang R, Hou DX, Chen X, Zhang CY, et al. Identification of mouse liver mitochondria-associated miRNAs and their potential biological functions. Cell Res. 2010;20:1076–8.

    Article  PubMed  Google Scholar 

  51. Barrey E, Saint-Auret G, Bonnamy B, Damas D, Boyer O, Gidrol X. Pre-microRNA and mature microRNA in human mitochondria. PLoS One. 2011;6:e20220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Zhang X, Zuo X, Yang B, Li Z, Xue Y, Zhou Y, et al. MicroRNA directly enhances mitochondrial translation during muscle differentiation. Cell. 2014;158:607–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Bandiera S, Ruberg S, Girard M, Cagnard N, Hanein S, Chretien D, et al. Nuclear outsourcing of RNA interference components to human mitochondria. PLoS One. 2011;6:e20746.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Das S, Ferlito M, Kent OA, Fox-Talbot K, Wang R, Liu D, et al. Nuclear miRNA regulates the mitochondrial genome in the heart. Circ Res. 2012;110:1596–603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Sripada L, Tomar D, Singh R. Mitochondria: one of the destinations of miRNAs. Mitochondrion. 2012;12:593–9.

    Article  CAS  PubMed  Google Scholar 

  56. Hwang HS, Kim HA. Chondrocyte apoptosis in the pathogenesis of osteoarthritis. Int J Mol Sci. 2015;16:26035–54.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Nugent M. MicroRNAs: exploring new horizons in osteoarthritis. Osteoarthritis Cartilage 2015.

  58. Li M, Marin-Muller C, Bharadwaj U, Chow KH, Yao Q, Chen C. MicroRNAs: control and loss of control in human physiology and disease. World J Surg. 2009;33:667–84.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Liu X, Chen X, Yu X, Tao Y, Bode AM, Dong Z, et al. Regulation of microRNAs by epigenetics and their interplay involved in cancer. J Exp Clin Cancer Res. 2013;32:96.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Ryan BM, Robles AI, Harris CC. Genetic variation in microRNA networks: the implications for cancer research. Nat Rev Cancer. 2010;10:389–402.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Ameres SL, Zamore PD. Diversifying microRNA sequence and function. Nat Rev Mol Cell Biol. 2013;14:475–88.

    Article  CAS  PubMed  Google Scholar 

  62. Kim B, Ha M, Loeff L, Chang H, Simanshu DK, Li S, et al. TUT7 controls the fate of precursor microRNAs by using three different uridylation mechanisms. EMBO J. 2015;34:1801–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Lim J, Ha M, Chang H, Kwon SC, Simanshu DK, Patel DJ, et al. Uridylation by TUT4 and TUT7 marks mRNA for degradation. Cell. 2014;159:1365–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Tsialikas J, Romer-Seibert J. LIN28: roles and regulation in development and beyond. Development. 2015;142:2397–404.

    Article  CAS  PubMed  Google Scholar 

  65. Nishikura K. A-to-I editing of coding and non-coding RNAs by ADARs. Nat Rev Mol Cell Biol. 2016;17:83–96.

    Article  CAS  PubMed  Google Scholar 

  66. Yang W, Chendrimada TP, Wang Q, Higuchi M, Seeburg PH, Shiekhattar R, et al. Modulation of microRNA processing and expression through RNA editing by ADAR deaminases. Nat Struct Mol Biol. 2006;13:13–21.

    Article  CAS  PubMed  Google Scholar 

  67. Cui Y, Huang T, Zhang X. RNA editing of microRNA prevents RNA-induced silencing complex recognition of target mRNA. Open Biol 2015;5.

  68. Kim U, Wang Y, Sanford T, Zeng Y, Nishikura K. Molecular cloning of cDNA for double-stranded RNA adenosine deaminase, a candidate enzyme for nuclear RNA editing. Proc Natl Acad Sci U S A. 1994;91:11457–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Melcher T, Maas S, Herb A, Sprengel R, Seeburg PH, Higuchi M. A mammalian RNA editing enzyme. Nature. 1996;379:460–4.

    Article  CAS  PubMed  Google Scholar 

  70. Chen CX, Cho DS, Wang Q, Lai F, Carter KC, Nishikura K. A third member of the RNA-specific adenosine deaminase gene family, ADAR3, contains both single- and double-stranded RNA binding domains. RNA. 2000;6:755–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Hartner JC, Schmittwolf C, Kispert A, Muller AM, Higuchi M, Seeburg PH. Liver disintegration in the mouse embryo caused by deficiency in the RNA-editing enzyme ADAR1. J Biol Chem. 2004;279:4894–902.

    Article  CAS  PubMed  Google Scholar 

  72. Horsch M, Seeburg PH, Adler T, Aguilar-Pimentel JA, Becker L, Calzada-Wack J, et al. Requirement of the RNA-editing enzyme ADAR2 for normal physiology in mice. J Biol Chem. 2011;286:18614–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Slotkin W, Nishikura K. Adenosine-to-inosine RNA editing and human disease. Genome Med. 2013;5:105.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Kawahara Y, Megraw M, Kreider E, Iizasa H, Valente L, Hatzigeorgiou AG, et al. Frequency and fate of microRNA editing in human brain. Nucleic Acids Res. 2008;36:5270–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Xhemalce B, Robson SC, Kouzarides T. Human RNA methyltransferase BCDIN3D regulates microRNA processing. Cell. 2012;151:278–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Pritchard CC, Cheng HH, Tewari M. MicroRNA profiling: approaches and considerations. Nat Rev Genet. 2012;13:358–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.

    Article  CAS  PubMed  Google Scholar 

  78. Metzker ML. Sequencing technologies—the next generation. Nat Rev Genet. 2010;11:31–46.

    Article  CAS  PubMed  Google Scholar 

  79. Linsen SE, de Wit E, Janssens G, Heater S, Chapman L, Parkin RK, et al. Limitations and possibilities of small RNA digital gene expression profiling. Nat Methods. 2009;6:474–6.

    Article  CAS  PubMed  Google Scholar 

  80. Tian G, Yin X, Luo H, Xu X, Bolund L, Zhang X, et al. Sequencing bias: comparison of different protocols of microRNA library construction. BMC Biotechnol. 2010;10:64.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Bernstein E, Kim SY, Carmell MA, Murchison EP, Alcorn H, Li MZ, et al. Dicer is essential for mouse development. Nat Genet. 2003;35:215–7.

    Article  CAS  PubMed  Google Scholar 

  82. Fukuda T, Yamagata K, Fujiyama S, Matsumoto T, Koshida I, Yoshimura K, et al. DEAD-box RNA helicase subunits of the Drosha complex are required for processing of rRNA and a subset of microRNAs. Nat Cell Biol. 2007;9:604–11.

    Article  CAS  PubMed  Google Scholar 

  83. Wang Y, Medvid R, Melton C, Jaenisch R, Blelloch R. DGCR8 is essential for microRNA biogenesis and silencing of embryonic stem cell self-renewal. Nat Genet. 2007;39:380–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kobayashi T, Lu J, Cobb BS, Rodda SJ, McMahon AP, Schipani E, et al. Dicer-dependent pathways regulate chondrocyte proliferation and differentiation. Proc Natl Acad Sci U S A. 2008;105:1949–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Kobayashi T, Papaioannou G, Mirzamohammadi F, Kozhemyakina E, Zhang M, Blelloch R, et al. Early postnatal ablation of the microRNA-processing enzyme, Drosha, causes chondrocyte death and impairs the structural integrity of the articular cartilage. Osteoarthr Cartil. 2015;23:1214–20. This article reveals the significance of Drosha in postnatal articular chondrocyte maintenance and integrity. The authors’ findings suggest that miRNAs are critical for articular chondrocyte survival and integrity of the cartilage matrix.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Miyaki S, Sato T, Inoue A, Otsuki S, Ito Y, Yokoyama S, et al. MicroRNA-140 plays dual roles in both cartilage development and homeostasis. Genes Dev. 2010;24:1173–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Iliopoulos D, Malizos KN, Oikonomou P, Tsezou A. Integrative microRNA and proteomic approaches identify novel osteoarthritis genes and their collaborative metabolic and inflammatory networks. PLoS One. 2008;3:e3740.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Jones SW, Watkins G, Le Good N, Roberts S, Murphy CL, Brockbank SM, et al. The identification of differentially expressed microRNA in osteoarthritic tissue that modulate the production of TNF-alpha and MMP13. Osteoarthr Cartil. 2009;17:464–72.

    Article  CAS  PubMed  Google Scholar 

  89. Akhtar N, Rasheed Z, Ramamurthy S, Anbazhagan AN, Voss FR, Haqqi TM. MicroRNA-27b regulates the expression of matrix metalloproteinase 13 in human osteoarthritis chondrocytes. Arthritis Rheum. 2010;62:1361–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Diaz-Prado S, Cicione C, Muinos-Lopez E, Hermida-Gomez T, Oreiro N, Fernandez-Lopez C, et al. Characterization of microRNA expression profiles in normal and osteoarthritic human chondrocytes. BMC Musculoskelet Disord. 2012;13:144.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Borgonio Cuadra VM, Gonzalez-Huerta NC, Romero-Cordoba S, Hidalgo-Miranda A, Miranda-Duarte A. Altered expression of circulating microRNA in plasma of patients with primary osteoarthritis and in silico analysis of their pathways. PLoS ONE. 2014;9:e97690. This article identifies newly discovered miRNAs in patient plasma in subjects with primary OA, and describes the biological significance of each identified miRNA based on in silico analysis. Overall this article identifies a set of miRNAs that may be identified as potential biomarkers when testing for OA in patient plasma.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Blasioli DJ, Kaplan DL. The roles of catabolic factors in the development of osteoarthritis. Tissue Eng Part B Rev. 2014;20:355–63.

    Article  CAS  PubMed  Google Scholar 

  93. Rahmati M, Mobasheri A, Mozafari M. Inflammatory mediators in osteoarthritis: a critical review of the state of the art, prospects, and future challenges. Bone 2016.

  94. Li ZC, Han N, Li X, Li G, Liu YZ, Sun GX, et al. Decreased expression of microRNA-130a correlates with TNF-alpha in the development of osteoarthritis. Int J Clin Exp Pathol. 2015;8:2555–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Santini P, Politi L, Vedova PD, Scandurra R, Scotto d'Abusco A. The inflammatory circuitry of miR-149 as a pathological mechanism in osteoarthritis. Rheumatol Int. 2014;34:711–6.

    Article  CAS  PubMed  Google Scholar 

  96. Makki MS, Haseeb A, Haqqi TM. MicroRNA-9 promotion of interleukin-6 expression by inhibiting monocyte chemoattractant protein-induced protein 1 expression in interleukin-1beta-stimulated human chondrocytes. Arthritis Rheumatol. 2015;67:2117–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Makki MS, Haqqi TM. miR-139 modulates MCPIP1/IL-6 expression and induces apoptosis in human OA chondrocytes. Exp Mol Med. 2015;47:e189.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Qi Y, Ma N, Yan F, Yu Z, Wu G, Qiao Y, et al. The expression of intronic miRNAs, miR-483 and miR-483*, and their host gene, Igf2, in murine osteoarthritis cartilage. Int J Biol Macromol. 2013;61:43–9.

    Article  CAS  PubMed  Google Scholar 

  99. Akhtar N, Haqqi TM. MicroRNA-199a* regulates the expression of cyclooxygenase-2 in human chondrocytes. Ann Rheum Dis. 2012;71:1073–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Park SJ, Cheon EJ, Kim HA. MicroRNA-558 regulates the expression of cyclooxygenase-2 and IL-1beta-induced catabolic effects in human articular chondrocytes. Osteoarthr Cartil. 2013;21:981–9.

    Article  CAS  PubMed  Google Scholar 

  101. Kulkarni RR, Patki PS, Jog VP, Gandage SG, Patwardhan B. Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol. 1991;33:91–5.

    Article  CAS  PubMed  Google Scholar 

  102. Grover AK, Samson SE. Benefits of antioxidant supplements for knee osteoarthritis: rationale and reality. Nutr J. 2016;15:1.

    Article  PubMed  PubMed Central  Google Scholar 

  103. Kim JH, Kim SJ. Overexpression of microRNA-25 by withaferin A induces cyclooxygenase-2 expression in rabbit articular chondrocytes. J Pharmacol Sci. 2014;125:83–90.

    Article  CAS  PubMed  Google Scholar 

  104. Tardif G, Hum D, Pelletier JP, Duval N, Martel-Pelletier J. Regulation of the IGFBP-5 and MMP-13 genes by the microRNAs miR-140 and miR-27a in human osteoarthritic chondrocytes. BMC Musculoskelet Disord. 2009;10:148.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Vonk LA, Kragten AH, Dhert WJ, Saris DB, Creemers LB. Overexpression of hsa-miR-148a promotes cartilage production and inhibits cartilage degradation by osteoarthritic chondrocytes. Osteoarthr Cartil. 2014;22:145–53.

    Article  CAS  PubMed  Google Scholar 

  106. Meng F, Zhang Z, Chen W, Huang G, He A, Hou C, et al. MicroRNA-320 regulates matrix metalloproteinase-13 expression in chondrogenesis and interleukin-1beta-induced chondrocyte responses. Osteoarthr Cartil 2016.

  107. Park SJ, Cheon EJ, Lee MH, Kim HA. MicroRNA-127-5p regulates matrix metalloproteinase 13 expression and interleukin-1 beta-induced catabolic effects in human chondrocytes. Arthritis Rheum. 2013;65:3141–52.

    Article  CAS  PubMed  Google Scholar 

  108. Wang G, Zhang Y, Zhao X, Meng C, Ma L, Kong Y. MicroRNA-411 inhibited matrix metalloproteinase 13 expression in human chondrocytes. Am J Transl Res. 2015;7:2000–6.

    PubMed  PubMed Central  Google Scholar 

  109. Liang ZJ, Zhuang H, Wang GX, Li Z, Zhang HT, Yu TQ, et al. MiRNA-140 is a negative feedback regulator of MMP-13 in IL-1beta-stimulated human articular chondrocyte C28/I2 cells. Inflamm Res. 2012;61:503–9.

    Article  CAS  PubMed  Google Scholar 

  110. Song J, Lee M, Kim D, Han J, Chun CH, Jin EJ. MicroRNA-181b regulates articular chondrocytes differentiation and cartilage integrity. Biochem Biophys Res Commun. 2013;431:210–4.

    Article  CAS  PubMed  Google Scholar 

  111. Ham O, Lee CY, Song BW, Lee SY, Kim R, Park JH, et al. Upregulation of miR-23b enhances the autologous therapeutic potential for degenerative arthritis by targeting PRKACB in synovial fluid-derived mesenchymal stem cells from patients. Mol Cells. 2014;37:449–56.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Philipot D, Guerit D, Platano D, Chuchana P, Olivotto E, Espinoza F, et al. p16INK4a and its regulator miR-24 link senescence and chondrocyte terminal differentiation-associated matrix remodeling in osteoarthritis. Arthritis Res Ther. 2014;16:R58.

    Article  PubMed  PubMed Central  Google Scholar 

  113. Ji Q, Xu X, Xu Y, Fan Z, Kang L, Li L, et al. miR-105/Runx2 axis mediates FGF2-induced ADAMTS expression in osteoarthritis cartilage. J Mol Med (Berl) 2016.

  114. 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. Int J Mol Med 2015.

  115. Ukai T, Sato M, Akutsu H, Umezawa A, Mochida J. MicroRNA-199a-3p, microRNA-193b, and microRNA-320c are correlated to aging and regulate human cartilage metabolism. J Orthop Res. 2012;30:1915–22.

    Article  CAS  PubMed  Google Scholar 

  116. Tsirimonaki E, Fedonidis C, Pneumaticos SG, Tragas AA, Michalopoulos I, Mangoura D. PKCepsilon signalling activates ERK1/2, and regulates aggrecan, ADAMTS5, and miR377 gene expression in human nucleus pulposus cells. PLoS One. 2013;8:e82045.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  117. Zheng H, Chen C. Body mass index and risk of knee osteoarthritis: systematic review and meta-analysis of prospective studies. BMJ Open. 2015;5:e007568.

    Article  PubMed  PubMed Central  Google Scholar 

  118. Koskinen A, Vuolteenaho K, Nieminen R, Moilanen T, Moilanen E. Leptin enhances MMP-1, MMP-3 and MMP-13 production in human osteoarthritic cartilage and correlates with MMP-1 and MMP-3 in synovial fluid from OA patients. Clin Exp Rheumatol. 2011;29:57–64.

    PubMed  Google Scholar 

  119. Wang X, Hunter D, Xu J, Ding C. Metabolic triggered inflammation in osteoarthritis. Osteoarthr Cartil. 2015;23:22–30. This review highlights the role metabolic factors and miRNAs play in inflammation and osteoarthritis. Furthermore the authors describe a major role for metabolic miRNAs and inflammation to explain the relationship between obesity and OA pathology.

    Article  CAS  PubMed  Google Scholar 

  120. Tsezou A, Iliopoulos D, Malizos KN, Simopoulou T. Impaired expression of genes regulating cholesterol efflux in human osteoarthritic chondrocytes. J Orthop Res. 2010;28:1033–9.

    CAS  PubMed  Google Scholar 

  121. Kostopoulou F, Gkretsi V, Malizos KN, Iliopoulos D, Oikonomou P, Poultsides L, et al. Central role of SREBP-2 in the pathogenesis of osteoarthritis. PLoS One. 2012;7:e35753.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Kostopoulou F, Malizos KN, Papathanasiou I, Tsezou A. MicroRNA-33a regulates cholesterol synthesis and cholesterol efflux-related genes in osteoarthritic chondrocytes. Arthritis Res Ther. 2015;17:42. This manuscript describes the role of miRNA-33a, a master regulator of cholesterol and fatty acid metabolism, during OA pathogenesis. The article describes a relationship between a microRNA important for metabolism and its role in OA progression.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Xie Q, Wei M, Kang X, Liu D, Quan Y, Pan X, et al. Reciprocal inhibition between miR-26a and NF-kappaB regulates obesity-related chronic inflammation in chondrocytes. Biosci Rep 2015.

  124. Adams CS, Horton Jr WE. Chondrocyte apoptosis increases with age in the articular cartilage of adult animals. Anat Rec. 1998;250:418–25.

    Article  CAS  PubMed  Google Scholar 

  125. Horton Jr WE, Feng L, Adams C. Chondrocyte apoptosis in development, aging and disease. Matrix Biol. 1998;17:107–15.

    Article  CAS  PubMed  Google Scholar 

  126. Abouheif MM, Nakasa T, Shibuya H, Niimoto T, Kongcharoensombat W, Ochi M. Silencing microRNA-34a inhibits chondrocyte apoptosis in a rat osteoarthritis model in vitro. Rheumatology (Oxford). 2010;49:2054–60.

    Article  CAS  Google Scholar 

  127. Li J, Huang J, Dai L, Yu D, Chen Q, Zhang X, et al. miR-146a, an IL-1beta responsive miRNA, induces vascular endothelial growth factor and chondrocyte apoptosis by targeting Smad4. Arthritis Res Ther. 2012;14:R75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Jin L, Zhao J, Jing W, Yan S, Wang X, Xiao C, et al. Role of miR-146a in human chondrocyte apoptosis in response to mechanical pressure injury in vitro. Int J Mol Med. 2014;34:451–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Song J, Kim D, Chun CH, Jin EJ. MicroRNA-9 regulates survival of chondroblasts and cartilage integrity by targeting protogenin. Cell Commun Signal. 2013;11:66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Kim D, Song J, Ahn C, Kang Y, Chun CH, Jin EJ. Peroxisomal dysfunction is associated with up-regulation of apoptotic cell death via miR-223 induction in knee osteoarthritis patients with type 2 diabetes mellitus. Bone. 2014;64:124–31.

    Article  CAS  PubMed  Google Scholar 

  131. Li YT, Chen SY, Wang CR, Liu MF, Lin CC, Jou IM, et al. Brief report: amelioration of collagen-induced arthritis in mice by lentivirus-mediated silencing of microRNA-223. Arthritis Rheum. 2012;64:3240–5.

    Article  CAS  PubMed  Google Scholar 

  132. Lin HS, Hu CY, Chan HY, Liew YY, Huang HP, Lepescheux L, et al. Anti-rheumatic activities of histone deacetylase (HDAC) inhibitors in vivo in collagen-induced arthritis in rodents. Br J Pharmacol. 2007;150:862–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Blanchard F, Chipoy C. Histone deacetylase inhibitors: new drugs for the treatment of inflammatory diseases? Drug Discov Today. 2005;10:197–204.

    Article  CAS  PubMed  Google Scholar 

  134. Song J, Jin EH, Kim D, Kim KY, Chun CH, Jin EJ. MicroRNA-222 regulates MMP-13 via targeting HDAC-4 during osteoarthritis pathogenesis. BBA Clin. 2015;3:79–89.

    Article  PubMed  Google Scholar 

  135. Pan G, Bauer JH, Haridas V, Wang S, Liu D, Yu G, et al. Identification and functional characterization of DR6, a novel death domain-containing TNF receptor. FEBS Lett. 1998;431:351–6.

    Article  CAS  PubMed  Google Scholar 

  136. Zhang D, Cao X, Li J, Zhao G. MiR-210 inhibits NF-kappaB signaling pathway by targeting DR6 in osteoarthritis. Sci Rep. 2015;5:12775.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Karlsson C, Dehne T, Lindahl A, Brittberg M, Pruss A, Sittinger M, et al. Genome-wide expression profiling reveals new candidate genes associated with osteoarthritis. Osteoarthr Cartil. 2010;18:581–92.

    Article  CAS  PubMed  Google Scholar 

  138. Zhang FJ, Luo W, Lei GH. Role of HIF-1alpha and HIF-2alpha in osteoarthritis. Joint Bone Spine. 2015;82:144–7.

    Article  CAS  PubMed  Google Scholar 

  139. Bai R, Zhao AQ, Zhao ZQ, Liu WL, Jian DM. MicroRNA-195 induced apoptosis in hypoxic chondrocytes by targeting hypoxia-inducible factor 1 alpha. Eur Rev Med Pharmacol Sci. 2015;19:545–51.

    CAS  PubMed  Google Scholar 

  140. Carames B, Taniguchi N, Otsuki S, Blanco FJ, Lotz M. Autophagy is a protective mechanism in normal cartilage, and its aging-related loss is linked with cell death and osteoarthritis. Arthritis Rheum. 2010;62:791–801.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Carames B, Hasegawa A, Taniguchi N, Miyaki S, Blanco FJ, Lotz M. Autophagy activation by rapamycin reduces severity of experimental osteoarthritis. Ann Rheum Dis. 2012;71:575–81.

    Article  CAS  PubMed  Google Scholar 

  142. Bouderlique T, Vuppalapati KK, Newton PT, Li L, Barenius B, Chagin AS. Targeted deletion of Atg5 in chondrocytes promotes age-related osteoarthritis. Ann Rheum Dis 2015.

  143. Zhang F, Wang J, Chu J, Yang C, Xiao H, Zhao C, et al. MicroRNA-146a induced by hypoxia promotes chondrocyte autophagy through Bcl-2. Cell Physiol Biochem. 2015;37:1442–53.

    Article  CAS  PubMed  Google Scholar 

  144. Kurowska-Stolarska M, Alivernini S, Ballantine LE, Asquith DL, Millar NL, Gilchrist DS, et al. MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis. Proc Natl Acad Sci U S A. 2011;108:11193–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. D’Adamo S, Alvarez-Garcia O, Muramatsu Y, Flamigni F, Lotz MK. MicroRNA-155 suppresses autophagy in chondrocytes by modulating expression of autophagy proteins. Osteoarthritis Cartilage 2016. This article describes the role of miRNA-155 in autophagy and OA chondrocytes. Overall this article links a specific miRNA to autophagy dysfunction that contributes to the OA phenotype.

  146. Song J, Ahn C, Chun CH, Jin EJ. A long non-coding RNA, GAS5, plays a critical role in the regulation of miR-21 during osteoarthritis. J Orthop Res. 2014;32:1628–35.

    Article  CAS  PubMed  Google Scholar 

  147. Le LT, Swingler TE, Crowe N, Vincent TL, Barter MJ, Donell ST, et al. The microRNA-29 family in cartilage homeostasis and osteoarthritis. J Mol Med (Berl) 2015.

  148. Akhtar N, Makki MS, Haqqi TM. MicroRNA-602 and microRNA-608 regulate sonic hedgehog expression via target sites in the coding region in human chondrocytes. Arthritis Rheumatol. 2015;67:423–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Li L, Jia J, Liu X, Yang S, Ye S, Yang W, et al. MicroRNA-16-5p controls development of osteoarthritis by targeting SMAD3 in chondrocytes. Curr Pharm Des. 2015;21:5160–7.

    Article  CAS  PubMed  Google Scholar 

  150. Zhong N, Sun J, Min Z, Zhao W, Zhang R, Wang W, et al. MicroRNA-337 is associated with chondrogenesis through regulating TGFBR2 expression. Osteoarthr Cartil. 2012;20:593–602.

    Article  CAS  PubMed  Google Scholar 

  151. Hou C, Yang Z, Kang Y, Zhang Z, Fu M, He A, et al. MiR-193b regulates early chondrogenesis by inhibiting the TGF-beta2 signaling pathway. FEBS Lett. 2015;589:1040–7.

    Article  CAS  PubMed  Google Scholar 

  152. Dai L, Zhang X, Hu X, Zhou C, Ao Y. Silencing of microRNA-101 prevents IL-1beta-induced extracellular matrix degradation in chondrocytes. Arthritis Res Ther. 2012;14:R268.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Steck E, Boeuf S, Gabler J, Werth N, Schnatzer P, Diederichs S, et al. Regulation of H19 and its encoded microRNA-675 in osteoarthritis and under anabolic and catabolic in vitro conditions. J Mol Med (Berl). 2012;90:1185–95.

    Article  CAS  Google Scholar 

  154. 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). J Biol Chem. 2012;287:916–24.

    Article  CAS  PubMed  Google Scholar 

  155. Umeda M, Terao F, Miyazaki K, Yoshizaki K, Takahashi I. MicroRNA-200a regulates the development of mandibular condylar cartilage. J Dent Res. 2015;94:795–802.

    Article  CAS  PubMed  Google Scholar 

  156. Seidl CI, Martinez-Sanchez A, Murphy CL. Derepression of microRNA-138 contributes to loss of the human articular chondrocyte phenotype. Arthritis Rheumatol. 2016;68:398–409.

    Article  CAS  PubMed  Google Scholar 

  157. Li L, Yang C, Liu X, Yang S, Ye S, Jia J, et al. Elevated expression of microRNA-30b in osteoarthritis and its role in ERG regulation of chondrocyte. Biomed Pharmacother. 2015;76:94–9.

    Article  CAS  PubMed  Google Scholar 

  158. Zhang Y, Xie RL, Croce CM, Stein JL, Lian JB, van Wijnen AJ, et al. A program of microRNAs controls osteogenic lineage progression by targeting transcription factor Runx2. Proc Natl Acad Sci U S A. 2011;108:9863–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Yang M, Zhang L, Gibson GJ. Chondrocyte miRNAs 221 and 483-5p respond to loss of matrix interaction by modulating proliferation and matrix synthesis. Connect Tissue Res. 2015;56:236–43.

    Article  CAS  PubMed  Google Scholar 

  160. Hinoi E, Bialek P, Chen YT, Rached MT, Groner Y, Behringer RR, et al. Runx2 inhibits chondrocyte proliferation and hypertrophy through its expression in the perichondrium. Genes Dev. 2006;20:2937–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Loughlin J, Reynard LN. Osteoarthritis: epigenetics of articular cartilage in knee and hip OA. Nat Rev Rheumatol. 2015;11:6–7. This article reviews several epigenetic mechanisms involved in regulating OA pathology.

    Article  CAS  PubMed  Google Scholar 

  162. Ideno H, Shimada A, Imaizumi K, Kimura H, Abe M, Nakashima K, et al. Predominant expression of H3K9 methyltransferases in prehypertrophic and hypertrophic chondrocytes during mouse growth plate cartilage development. Gene Expr Patterns. 2013;13:84–90.

    Article  CAS  PubMed  Google Scholar 

  163. Yang L, Lawson KA, Teteak CJ, Zou J, Hacquebord J, Patterson D, et al. ESET histone methyltransferase is essential to hypertrophic differentiation of growth plate chondrocytes and formation of epiphyseal plates. Dev Biol. 2013;380:99–110.

    Article  CAS  PubMed  Google Scholar 

  164. Song J, Kim D, Chun CH, Jin EJ. miR-370 and miR-373 regulate the pathogenesis of osteoarthritis by modulating one-carbon metabolism via SHMT-2 and MECP-2, respectively. Aging Cell. 2015;14:826–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  165. Hartmann P, Zhou Z, Natarelli L, Wei Y, Nazari-Jahantigh M, Zhu M, et al. Endothelial Dicer promotes atherosclerosis and vascular inflammation by miRNA-103-mediated suppression of KLF4. Nat Commun. 2016;7:10521.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. An F, Gong B, Wang H, Yu D, Zhao G, Lin L, et al. miR-15b and miR-16 regulate TNF mediated hepatocyte apoptosis via BCL2 in acute liver failure. Apoptosis. 2012;17:702–16.

    Article  CAS  PubMed  Google Scholar 

  167. Chu TH, Yang CC, Liu CJ, Lui MT, Lin SC, Chang KW. miR-211 promotes the progression of head and neck carcinomas by targeting TGFbetaRII. Cancer Lett. 2013;337:115–24.

    Article  CAS  PubMed  Google Scholar 

  168. Crippa E, Lusa L, De Cecco L, Marchesi E, Calin GA, Radice P, et al. miR-342 regulates BRCA1 expression through modulation of ID4 in breast cancer. PLoS ONE. 2014;9, e87039.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  169. Afanasyeva EA, Mestdagh P, Kumps C, Vandesompele J, Ehemann V, Theissen J, et al. MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival. Cell Death Differ. 2011;18:974–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Chen QG, Zhou W, Han T, Du SQ, Li ZH, Zhang Z, et al. MiR-345 suppresses proliferation, migration and invasion by targeting Smad1 in human prostate cancer. J Cancer Res Clin Oncol. 2016;142:213–24.

    Article  CAS  PubMed  Google Scholar 

  171. Harris TA, Yamakuchi M, Ferlito M, Mendell JT, Lowenstein CJ. MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1. Proc Natl Acad Sci U S A. 2008;105:1516–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  172. Jing W, Jiang W. MicroRNA-93 regulates collagen loss by targeting MMP3 in human nucleus pulposus cells. Cell Prolif. 2015;48:284–92.

    Article  CAS  PubMed  Google Scholar 

  173. Xue TM, Tao LD, Zhang M, Xu GC, Zhang J, Zhang PJ. miR-20b overexpression is predictive of poor prognosis in gastric cancer. OncoTargets Ther. 2015;8:1871–6.

    Article  Google Scholar 

  174. Hu J, Lv G, Zhou S, Zhou Y, Nie B, Duan H, et al. The down regulation of MiR-182 is associated with the growth and invasion of osteosarcoma cells through the regulation of TIAM1 expression. PLoS ONE. 2015;10, e0121175.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  175. Li W, Wang P, Zhang Z, Wang W, Liu Y, Qi Q. miR-184 regulates proliferation in nucleus pulposus cells by targeting GAS1. World Neurosurg. 2016.

  176. Wang H, Zhu Y, Zhao M, Wu C, Zhang P, Tang L, et al. miRNA-29c suppresses lung cancer cell adhesion to extracellular matrix and metastasis by targeting integrin beta1 and matrix metalloproteinase2 (MMP2). PLoS ONE. 2013;8, e70192.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  177. Liu C, Cheng H, Shi S, Cui X, Yang J, Chen L, et al. MicroRNA-34b inhibits pancreatic cancer metastasis through repressing Smad3. Curr Mol Med. 2013;13:467–78.

    Article  CAS  PubMed  Google Scholar 

  178. Ji ML, Lu J, Shi PL, Zhang XJ, Wang SZ, Chang Q, et al. Dysregulated miR-98 contributes to extracellular matrix degradation by targeting IL-6/STAT3 signalling pathway in human intervertebral disc degeneration. J Bone Miner Res 2015.

  179. Rieger JK, Reutter S, Hofmann U, Schwab M, Zanger UM. Inflammation-associated microRNA-130b down-regulates cytochrome P450 activities and directly targets CYP2C9. Drug Metab Dispos. 2015;43:884–8.

    Article  CAS  PubMed  Google Scholar 

  180. Cong J, Liu R, Wang X, Jiang H, Zhang Y. MiR-634 decreases cell proliferation and induces apoptosis by targeting mTOR signaling pathway in cervical cancer cells. Artif Cells Nanomed Biotechnol. 2015; 1–8.

  181. Uchino K, Takeshita F, Takahashi RU, Kosaka N, Fujiwara K, Naruoka H, et al. Therapeutic effects of microRNA-582-5p and -3p on the inhibition of bladder cancer progression. Mol Ther. 2013;21:610–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Meng S, Cao J, Wang L, Zhou Q, Li Y, Shen C, et al. MicroRNA 107 partly inhibits endothelial progenitor cells differentiation via HIF-1beta. PLoS One. 2012;7:e40323.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Thoms BL, Dudek KA, Lafont JE, Murphy CL. Hypoxia promotes the production and inhibits the destruction of human articular cartilage. Arthritis Rheum. 2013;65:1302–12.

    Article  CAS  PubMed  Google Scholar 

  184. Schipani E, Ryan HE, Didrickson S, Kobayashi T, Knight M, Johnson RS. Hypoxia in cartilage: HIF-1alpha is essential for chondrocyte growth arrest and survival. Genes Dev. 2001;15:2865–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  185. Li Z, Rana TM. Therapeutic targeting of microRNAs: current status and future challenges. Nat Rev Drug Discov. 2014;13:622–38. This review describes the use of miRNAs as treatment strategies. Topics that are discussed include design, modification, challenges, and delivery methods. The authors also review the current progress of using miRNA-targeted therapies for clinical use.

    Article  CAS  PubMed  Google Scholar 

  186. Li W, Cai L, Zhang Y, Cui L, Shen G. Intra-articular resveratrol injection prevents osteoarthritis progression in a mouse model by activating SIRT1 and thereby silencing HIF-2alpha. J Orthop Res. 2015;33:1061–70.

    Article  CAS  PubMed  Google Scholar 

  187. Liang Q, Wang XP, Chen TS. Resveratrol protects rabbit articular chondrocyte against sodium nitroprusside-induced apoptosis via scavenging ROS. Apoptosis. 2014;19:1354–63.

    Article  CAS  PubMed  Google Scholar 

  188. Liu L, Gu H, Liu H, Jiao Y, Li K, Zhao Y, et al. Protective effect of resveratrol against IL-1beta-induced inflammatory response on human osteoarthritic chondrocytes partly via the TLR4/MyD88/NF-kappaB signaling pathway: an "in vitro study". Int J Mol Sci. 2014;15:6925–40.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  189. Latruffe N, Lancon A, Frazzi R, Aires V, Delmas D, Michaille JJ, et al. Exploring new ways of regulation by resveratrol involving miRNAs, with emphasis on inflammation. Ann N Y Acad Sci. 2015;1348:97–106.

    Article  CAS  PubMed  Google Scholar 

  190. Tili E, Michaille JJ, Adair B, Alder H, Limagne E, Taccioli C, et al. Resveratrol decreases the levels of miR-155 by upregulating miR-663, a microRNA targeting JunB and JunD. Carcinogenesis. 2010;31:1561–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Tili E, Michaille JJ, Cimino A, Costinean S, Dumitru CD, Adair B, et al. Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol. 2007;179:5082–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tariq M. Haqqi.

Ethics declarations

Conflict of Interest

GRS and TMH declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Funding

This work was supported in part by USPHS/NIH grants (RO1 AT007373, RO1 AT005520, RO1 AR067056, R21 AR064890) and funds from Northeast Ohio Medical University to TMH.

Additional information

This article is part of the Topical Collection on Osteoarthritis

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sondag, G.R., Haqqi, T.M. The Role of MicroRNAs and Their Targets in Osteoarthritis. Curr Rheumatol Rep 18, 56 (2016). https://doi.org/10.1007/s11926-016-0604-x

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11926-016-0604-x

Keywords

Navigation