Volume 23, Issue 3 (2020)                   Pathobiol Res 2020, 23(3): 165-176 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Akbari Moghadam N, Bagheri F, Baghaban Eslaminejad M. Inhibiting the Degeneration of Injured Cartilage Matrix by Using the RNA Interference Technology: New Horizons in Osteoarthritis Treatment. Pathobiol Res. 2020; 23 (3) :165-176
URL: http://mjms.modares.ac.ir/article-30-41611-en.html
1- Department of Biomedical Engineering, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran
2- Department of Biotechnology, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran , f.bagheri@modares.ac.ir
3- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Abstract:   (384 Views)
Osteoarthritis is the most common articular disease that has significantly affected the patients’ quality of life. As cartilage doesn’t have any blood vessels and neurons, its treatment is a difficult task to do. Traditional therapeutic approaches, including the use of non-steroidal anti-inflammatory drugs (NSAIDs) and surgical interventions, can only control the disease, and the joint will lose its functionality after a short period. Consequently, modern methods such as cell therapy and tissue engineering along with using various biomaterials are being attempted to repair degenerated cartilage tissue. Using interfering RNAs is another approach that targets specific destructive or malfunctioned RNA sequences and suppresses the responsible factors for cartilage tissue destruction. Hence, the degenerated tissue can gradually retain the balance between anabolic and catabolic activities. Identification of the affecting genes in degeneration or malfunctioning and their suppression has provided promising results for the treatment of diseases. In the current study, after introducing the tissue, the process of cartilage degeneration and osteoarthritis development, the researches that have investigated the effect of interfering RNAs on rehabilitating cartilage tissue via inhibition of cartilage matrix destruction are reviewed.
Full-Text [PDF 888 kb]   (48 Downloads)    
Article Type: Analytic Review | Subject: Cellular Pathology
Received: 2020/09/29 | Accepted: 2020/08/12 | Published: 2020/09/20
* Corresponding Author Address: Tarbiat Modares University, Nasr Bridge, Jalal-Al-Ahmad Highway, Tehran, Iran. Postal Code: 1411713185.

1. Zhang W, Ouyang H, Dass CR, Xu J. Current research on pharmacologic and regenerative therapies for osteoarthritis. Bone Res. 2016;4(1):15040. [Link] [DOI:10.1038/boneres.2015.40]
2. Sophia Fox AJ, Bedi A, Rodeo SA. The basic science of articular cartilage: Structure, composition, and function. Sports Health. 2009;1(6):461-8. [Link] [DOI:10.1177/1941738109350438]
3. Athanasiou KA, Darling EM, Hu JC, DuRaine GD, Reddi AH. Articular cartilage. Boca Raton: CRC Press; 2017. [Link] [DOI:10.1201/b14183]
4. Holyoak DT, Tian YF, Van Der Meulen MC, Singh A. Osteoarthritis: Pathology, mouse models, and nanoparticle injectable systems for targeted treatment. Ann Biomed Eng. 2016;44(6):2062-75. [Link] [DOI:10.1007/s10439-016-1600-z]
5. Cooke ME, Lawless BM, Jones SW, Grover LM. Matrix degradation in osteoarthritis primes the superficial region of cartilage for mechanical damage. Acta Biomater. 2018;78:320-8. [Link] [DOI:10.1016/j.actbio.2018.07.037]
6. Freitag J, Bates D, Boyd R, Shah K, Barnard A, Huguenin L, et al. Mesenchymal stem cell therapy in the treatment of osteoarthritis: reparative pathways, safety and efficacy-a review. BMC Musculoskelet Disord. 2016;17(1):230. [Link] [DOI:10.1186/s12891-016-1085-9]
7. Brown Sh, Kumar Sh, Sharma B. Intra-articular targeting of nanomaterials for the treatment of osteoarthritis. Acta Biomater. 2019;93:239-57. [Link] [DOI:10.1016/j.actbio.2019.03.010]
8. Marcacci M, Berruto M, Brocchetta D, Delcogliano A, Ghinelli D, Gobbi A, et al. Articular cartilage engineering with hyalograft (R) C: 3-year clinical results. Clin Orthop Relat Res 1976-2007. 2005;435:96-105. [Link] [DOI:10.1097/01.blo.0000165737.87628.5b]
9. Bian L, Zhai DY, Tous E, Rai R, Mauck RL, Burdick JA. Enhanced MSC chondrogenesis following delivery of TGF-β3 from alginate microspheres within hyaluronic acid hydrogels in vitro and in vivo. Biomaterials. 2011;32(27):6425-34. [Link] [DOI:10.1016/j.biomaterials.2011.05.033]
10. Buda R, Vannini F, Castagnini F, Cavallo M, Ruffilli A, Ramponi L, et al. Regenerative treatment in osteochondral lesions of the talus: Autologous chondrocyte implantation versus one-step bone marrow derived cells transplantation. Int Orthop. 2015;39(5):893-900. [Link] [DOI:10.1007/s00264-015-2685-y]
11. Madry H, Cucchiarini M. Advances and challenges in gene‐based approaches for osteoarthritis. J Gene Med. 2013;15(10):343-55. [Link] [DOI:10.1002/jgm.2741]
12. Safari F, Fani N, Eglin D, Alini M, Stoddart MJ, Baghaban Eslaminejad M. Human umbilical cord‐derived scaffolds for cartilage tissue engineering. J Biomed Mater Res Part A. 2019;107(8):1793-802. [Link] [DOI:10.1002/jbm.a.36698]
13. Shamekhi MA, Mirzadeh H, Mahdavi H, Rabiee A, Mohebbi-Kalhori D, Eslaminejad MB. Graphene oxide containing chitosan scaffolds for cartilage tissue engineering. Int J Biol Macromol. 2019;127:396-405. [Link] [DOI:10.1016/j.ijbiomac.2019.01.020]
14. Hosseini S, Eslaminejad MB, Bagheri F, Shamekhi MA. Tissue engineering: Polymeric scaffolds for MSC-Based cartilage. In: Mishra M. Encyclopedia of polymer applications. 1st Edition. Boca Raton: CRC Press; 2018. pp. 2683-703. [Link]
15. Lolli A, Penolazzi L, Narcisi R, Van Osch GJ, Piva R. Emerging potential of gene silencing approaches targeting anti-chondrogenic factors for cell-based cartilage repair. Cell Mol Life Sci. 2017;74(19):3451-65. [Link] [DOI:10.1007/s00018-017-2531-z]
16. Bagheri F, Safarian S, Eslaminejad MB, Sheibani N. siRNA-mediated knock-down of DFF45 amplifies doxorubicin therapeutic effects in breast cancer cells. Cell Oncol. 2013;36(6):515-26. [Link] [DOI:10.1007/s13402-013-0157-1]
17. Zahir-Jouzdani F, Mottaghitalab F, Dinarvand M, Atyabi F. siRNA delivery for treatment of degenerative diseases, new hopes and challenges. J Drug Deliv Sci Technol. 2018;45:428-41. [Link] [DOI:10.1016/j.jddst.2018.04.001]
18. Nasiri N, Hosseini S, Alini M, Khademhosseini A, Eslaminejad MB. Targeted cell delivery for articular cartilage regeneration and osteoarthritis treatment. Drug Discov Today. 2019;24(11):2212-24. [Link] [DOI:10.1016/j.drudis.2019.07.010]
19. Alexopoulos LG, Setton LA, Guilak F. The biomechanical role of the chondrocyte pericellular matrix in articular cartilage. Acta Biomater. 2005;1(3):317-25. [Link] [DOI:10.1016/j.actbio.2005.02.001]
20. Huber M, Trattnig S, Lintner F. Anatomy, biochemistry, and physiology of articular cartilage. Investig Radiol. 2000;35(10):573-80. [Link] [DOI:10.1097/00004424-200010000-00003]
21. Fuentes-Mera L, Camacho A, Moncada-Saucedo NK, Peña-Martínez V. Current applications of mesenchymal stem cells for cartilage tissue engineering. In: Pham PV. Mesenchymal stem cells-isolation, characterization and applications. Norderstedt: BOD; 2017. pp. 149-84. [Link] [DOI:10.5772/intechopen.68172]
22. Bajpayee AG, Grodzinsky AJ. Cartilage-targeting drug delivery: Can electrostatic interactions help?. Nat Rev Rheumatol. 2017;13(3):183. [Link] [DOI:10.1038/nrrheum.2016.210]
23. Antons J, Marascio MG, Nohava J, Martin R, Applegate LA, Bourban PE, et al. Zone-dependent mechanical properties of human articular cartilage obtained by indentation measurements. J Mater Sci Mater Med. 2018;29(5):57. [Link] [DOI:10.1007/s10856-018-6066-0]
24. Poole AR, Kojima T, Yasuda T, Mwale F, Kobayashi M, Laverty S. Composition and structure of articular cartilage: A template for tissue repair. Clin Orthop Relat Res. 2001;391:S26-33. [Link] [DOI:10.1097/00003086-200110001-00004]
25. Flik KR, Verma N, Cole BJ, Bach BR. Articular cartilage. In: Williams RJ. Cartilage repair strategies. Totowa: Humana Press; 2007. pp: 1-12. [Link] [DOI:10.1007/978-1-59745-343-1_1]
26. Maudens P, Jordan O, Allémann E. Recent advances in intra-articular drug delivery systems for osteoarthritis therapy. Drug Discov Today. 2018;23(10):1761-75. [Link] [DOI:10.1016/j.drudis.2018.05.023]
27. Glyn-Jones S, Palmer AJ, Agricola R, Price AJ, Vincent TL, Weinans H, et al. Osteoarthritis. Lancet. 2015;386(9991):376-87. [Link] [DOI:10.1016/S0140-6736(14)60802-3]
28. Marks R. Osteoarthritis and articular cartilage: Biomechanics and novel treatment paradigms. Adv Aging Res. 2014;3(04):297-309. [Link] [DOI:10.4236/aar.2014.34039]
29. Burrage PS, Mix KS, Brinckerhoff CE. Matrix metalloproteinases: Role in arthritis. Front Biosci. 2006;11(1):529-43. [Link] [DOI:10.2741/1817]
30. Sandell LJ, Aigner T. Articular cartilage and changes in arthritis: Cell biology of osteoarthritis. Arthritis Res Ther. 2001;3(2):107. [Link] [DOI:10.1186/ar148]
31. Makris EA, Gomoll AH, Malizos KN, Hu JC, Athanasiou KA. Repair and tissue engineering techniques for articular cartilage. Nat Rev Rheumatol. 2015;11(1):21. [Link] [DOI:10.1038/nrrheum.2014.157]
32. Ataie M, Solouk A, Bagheri F, Seyed Jafari E. Regeneration of musculoskeletal injuries using mesenchymal stem cells loaded scaffolds. Tehran Univ Med J TUMS Publ. 2017;75(4):241-50. [Persian] [Link]
33. Evans CH, Ghivizzani SC, Robbins PD. Arthritis gene therapy is becoming a reality. Nat Rev Rheumatol. 2018;14(7):381-2. [Link] [DOI:10.1038/s41584-018-0009-5]
34. Hannon GJ. RNA interference. Nature. 2002;418(6894):244-51. [Link] [DOI:10.1038/418244a]
35. Chen LX, Lin L, Wang HJ, Wei XL, Fu X, Zhang JY, et al. Suppression of early experimental osteoarthritis by in vivo delivery of the adenoviral vector-mediated NF-κBp65-specific siRNA. Osteoarthr Cartil. 2008;16(2):174-84. [Link] [DOI:10.1016/j.joca.2007.06.006]
36. Liu Sh. RNA interference ex vivo. In: Liu Sh, editor. Rheumatoid arthritis. Berlin: Springer; 2018. pp. 129-35. [Link] [DOI:10.1007/978-1-4939-8802-0_13]
37. Kim MJ, Park JS, Lee SJ, Jang J, Park JS, Back SH, et al. Notch1 targeting siRNA delivery nanoparticles for rheumatoid arthritis therapy. J Controll Release. 2015;216:140-8. [Link] [DOI:10.1016/j.jconrel.2015.08.025]
38. Tang G. siRNA and miRNA: An insight into RISCs. Trends Biochem Sci. 2005;30(2):106-14. [Link] [DOI:10.1016/j.tibs.2004.12.007]
39. Dana H, Chalbatani GM, Mahmoodzadeh H, Karimloo R, Rezaiean O, Moradzadeh A, et al. Molecular mechanisms and biological functions of siRNA. Int J Biomed Sci IJBS. 2017;13(2):48-57. [Link]
40. Grimm D. Small silencing RNAs: State-of-the-art. Adv Drug Deliv Rev. 2009;61(9):672-703. [Link] [DOI:10.1016/j.addr.2009.05.002]
41. Siomi H, Siomi MC. On the road to reading the RNA-interference code. Nature. 2009;457(7228):396-404. [Link] [DOI:10.1038/nature07754]
42. Aravin AA, Lagos-Quintana M, Yalcin A, Zavolan M, Marks D, Snyder B, et al. The small RNA profile during Drosophila melanogaster development. Dev Cell. 2003;5(2):337-50. [Link] [DOI:10.1016/S1534-5807(03)00228-4]
43. Brennecke J, Aravin AA, Stark A, Dus M, Kellis M, Sachidanandam R, et al. Discrete small RNA-generating loci as master regulators of transposon activity in Drosophila. Cell. 2007;128(6):1089-103. [Link] [DOI:10.1016/j.cell.2007.01.043]
44. Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nature Rev Genet. 2010;11(9):597-610. [Link] [DOI:10.1038/nrg2843]
45. 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):843-54. [Link] [DOI:10.1016/0092-8674(93)90529-Y]
46. Bartel DP. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281-97. [Link] [DOI:10.1016/S0092-8674(04)00045-5]
47. Xu W, Jiang X, Huang L. RNA interference technology. Compr Biotechnol. 2019:560-75. [Link]
48. Bagheri F, Safarian S, Eslaminejad MB. Overextension of DFF40 and down regulation of DFF45 for evaluation of apoptosis induction in breast cancer cells (T-47D cell line) in presence of doxorubicin and some sulfonamide drugs, in College of Science, School of Biology [Dissertation]. Tehran: University of Tehran; 2013. [Persian] [Link]
49. Jin L, Zeng X, Liu M, Deng Y, He N. Current progress in gene delivery technology based on chemical methods and nano-carriers. Theranostics. 2014;4(3):240-55. [Link] [DOI:10.7150/thno.6914]
50. Ramamoorth M, Narvekar A. Non viral vectors in gene therapy-an overview. J Clin Diagn Res JCDR. 2015;9(1):GE01-6. [Link] [DOI:10.7860/JCDR/2015/10443.5394]
51. Jakutavičiūtė M, Ruzgys P, Tamošiūnas M, Maciulevičius M, Šatkauskas S. Physical methods for drug and gene delivery through the cell plasma membrane. In: Kulbacka J, Satkauskas S, editors. Transport across natural and modified biological membranes and its implications in physiology and therapy. Berlin: Springer; 2017. pp. 73-92. [Link] [DOI:10.1007/978-3-319-56895-9_5]
52. Agi E, Mosaferi Z, Khatamsaz S, Cheraghi P, Samadian N, Bolhassani A. Different strategies of gene delivery for treatment of cancer and other disorders. J Solid Tumors. 2016;6:76-84. [Link] [DOI:10.5430/jst.v6n2p76]
53. Herrero MJ, Sendra L, Miguel A, Aliño SF. Physical methods of gene delivery. In: Brunetti-Pierri N, editor. Safety and efficacy of gene-based therapeutics for inherited disorders. Berlin: Springer; 2017. pp. 113-35. [Link] [DOI:10.1007/978-3-319-53457-2_6]
54. Deng Y, Wang CC, Choy KW, Du Q, Chen J, Wang Q, et al. Therapeutic potentials of gene silencing by RNA interference: Principles, challenges, and new strategies. Gene. 2014;538(2):217-27. [Link] [DOI:10.1016/j.gene.2013.12.019]
55. Nyamay'Antu A, Dumont M, Kedinger V, Erbacher P. Non-viral vector mediated gene delivery: The outsider to watch out for in gene therapy. Cell Gene Ther Insights. 2019;5:51-7. [Link] [DOI:10.18609/cgti.2019.007]
56. Inada M, Wang Y, Byrne MH, Rahman MU, Miyaura C, López-Otín C, et al. Critical roles for collagenase-3 (Mmp13) in development of growth plate cartilage and in endochondral ossification. Proc Natl Acad Sci. 2004;101(49):17192-7. [Link] [DOI:10.1073/pnas.0407788101]
57. Akagi R, Sasho T, Saito M, Endo J, Yamaguchi S, Muramatsu Y, et al. Effective knock down of matrix metalloproteinase‐13 by an intra‐articular injection of small interfering RNA (siRNA) in a murine surgically‐induced osteoarthritis model. J Orthop Res. 2014;32(9):1175-80. [Link] [DOI:10.1002/jor.22654]
58. Nakagawa R, Akagi R, Yamaguchi S, Enomoto T, Sato Y, Kimura S, et al. Single vs. repeated matrix metalloproteinase-13 knockdown with intra-articular short interfering RNA administration in a murine osteoarthritis model. Connect Tissue Res. 2019;60(4):335-43. [Link] [DOI:10.1080/03008207.2018.1539082]
59. Mokuda S, Nakamichi R, Matsuzaki T, Ito Y, Sato T, Miyata K, et al. Wwp2 maintains cartilage homeostasis through regulation of Adamts5. Nat Commun. 2019;10(1):2429. [Link] [DOI:10.1038/s41467-019-10177-1]
60. Chen P, Zhu Sh, Wang Y, Mu Q, Wu Y, Xia Q, et al. The amelioration of cartilage degeneration by ADAMTS-5 inhibitor delivered in a hyaluronic acid hydrogel. Biomaterials. 2014;35(9):2827-36. [Link] [DOI:10.1016/j.biomaterials.2013.12.076]
61. Chu X, You H, Yuan X, Zhao W, Li W, Guo X. Protective effect of lentivirus-mediated siRNA targeting ADAMTS-5 on cartilage degradation in a rat model of osteoarthritis. Int J Mol Med. 2013;31(5):1222-8. [Link] [DOI:10.3892/ijmm.2013.1318]
62. Zhang Q, Ji Q, Wang X, Kang L, Fu Y, Yin Y, et al. SOX9 is a regulator of ADAMTSs-induced cartilage degeneration at the early stage of human osteoarthritis. Osteoarthr Cartil. 2015;23(12):2259-68. [Link] [DOI:10.1016/j.joca.2015.06.014]
63. Garcia JP, Stein J, Cai Y, Riemers F, Wexselblatt E, Wengel J, et al. Fibrin-hyaluronic acid hydrogel-based delivery of antisense oligonucleotides for ADAMTS5 inhibition in co-delivered and resident joint cells in osteoarthritis. J Controll Release. 2019;294:247-58. [Link] [DOI:10.1016/j.jconrel.2018.12.030]
64. Xu J, Li J, Lin S, Wu T, Huang H, Zhang K, et al. Nanocarrier‐mediated codelivery of small molecular drugs and siRNA to enhance chondrogenic differentiation and suppress hypertrophy of human mesenchymal stem cells. Adv Funct Mater. 2016;26(15):2463-72. [Link] [DOI:10.1002/adfm.201504070]
65. Yano F, Ohba S, Murahashi Y, Tanaka S, Saito T, Chung UI. Runx1 contributes to articular cartilage maintenance by enhancement of cartilage matrix production and suppression of hypertrophic differentiation. Sci Rep. 2019;9(1):7666. [Link] [DOI:10.1038/s41598-019-43948-3]
66. Chen CG, Thuillier D, Chin EN, Alliston T. Chondrocyte‐intrinsic Smad3 represses Runx2‐inducible matrix metalloproteinase 13 expression to maintain articular cartilage and prevent osteoarthritis. Arthritis Rheum. 2012;64(10):3278-89. [Link] [DOI:10.1002/art.34566]
67. Yang S, Kim J, Ryu JH, Oh H, Chun CH, Kim BJ, et al. Hypoxia-inducible factor-2α is a catabolic regulator of osteoarthritic cartilage destruction. Nat Med. 2010;16(6):687-93. [Link] [DOI:10.1038/nm.2153]
68. Pi Y, Zhang X, Shao Z, Zhao F, Hu X, Ao Y. Intra-articular delivery of anti-Hif-2α siRNA by chondrocyte-homing nanoparticles to prevent cartilage degeneration in arthritic mice. Gene Ther. 2015;22(6):439-48. [Link] [DOI:10.1038/gt.2015.16]
69. Roman-Blas JA, Jimenez SA. NF-κB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. Osteoarthr Cartil. 2006;14(9):839-48. [Link] [DOI:10.1016/j.joca.2006.04.008]
70. Goldring MB, Otero M, Plumb DA, Dragomir C, Favero M, El Hachem K, et al. Roles of inflammatory and anabolic cytokines in cartilage metabolism: Signals and multiple effectors converge upon MMP-13 regulation in osteoarthritis. Eur Cells Mater. 2011;21:202-20. [Link] [DOI:10.22203/eCM.v021a16]
71. Yan H, Duan X, Pan H, Holguin N, Rai MF, Akk A, et al. Suppression of NF-κB activity via nanoparticle-based siRNA delivery alters early cartilage responses to injury. Proc Natl Acad Sci. 2016;113(41):E6199-208. [Link] [DOI:10.1073/pnas.1608245113]
72. Yan H, Duan X, Pan H, Akk A, Sandell LJ, Wickline SA, et al. Development of a peptide-siRNA nanocomplex targeting NF-κB for efficient cartilage delivery. Sci Rep. 2019;9(1):442. [Link] [DOI:10.1038/s41598-018-37018-3]
73. Wei F, Zhou J, Wei X, Zhang J, Fleming BC, Terek R, et al. Activation of Indian hedgehog promotes chondrocyte hypertrophy and upregulation of MMP-13 in human osteoarthritic cartilage. Osteoarthr Cartil. 2012;20(7):755-63. [Link] [DOI:10.1016/j.joca.2012.03.010]
74. Wang S, Wei X, Sun X, Chen C, Zhou J, Zhang G, et al. A novel therapeutic strategy for cartilage diseases based on lipid nanoparticle-RNAi delivery system. Int J Nanomed. 2018;13:617-31. [Link] [DOI:10.2147/IJN.S142797]

Add your comments about this article : Your username or Email:

Send email to the article author