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Molecular therapy : the journal of the American Society of Gene Therapy2017; 25(10); 2415-2426; doi: 10.1016/j.ymthe.2017.07.015

MicroRNA29a Treatment Improves Early Tendon Injury.

Abstract: Tendon injuries (tendinopathies) are common in human and equine athletes and characterized by dysregulated collagen matrix, resulting in tendon damage. We have previously demonstrated a functional role for microRNA29a (miR29a) as a post-transcriptional regulator of collagen 3 expression in murine and human tendon injury. Given the translational potential, we designed a randomized, blinded trial to evaluate the potential of a miR29a replacement therapy as a therapeutic option to treat tendinopathy in an equine model that closely mimics human disease. Tendon injury was induced in the superficial digital flexor tendon (SDFT) of 17 horses. Tendon lesions were treated 1 week later with an intralesional injection of miR29a or placebo. miR29a treatment reduced collagen 3 transcript levels at week 2, with no significant changes in collagen 1. The relative lesion cross-sectional area was significantly lower in miR29a tendons compared to control tendons. Histology scores were significantly better for miR29a-treated tendons compared to control tendons. These data support the mechanism of microRNA-mediated modulation of early pathophysiologic events that facilitate tissue remodeling in the tendon after injury and provides a strong proof of principle that a locally delivered miR29a therapy improves early tendon healing.
Publication Date: 2017-07-28 PubMed ID: 28822690PubMed Central: PMC5628866DOI: 10.1016/j.ymthe.2017.07.015Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article presents a study on the use of microRNA29a (miR29a) as a therapy to improve early tendon injury. The study was conducted on horses and found that miR29a reduced certain indicators of injury and facilitated improved healing.

Study Objectives

  • The main objective of this study was to investigate the potential of microRNA29a (miR29a) as a post-transcriptional regulator of collagen 3 expression in treating tendon injuries.
  • The study also aimed at evaluating the effectiveness of this therapeutic option in an equine model which closely mimics human tendon injuries.

Methodology

  • Tendon injuries were induced in the superficial digital flexor tendon (SDFT) of 17 horses.
  • These tendon lesions were treated a week later with an intralesional injection of miR29a or a placebo.
  • The team measured collagen 3 transcript levels, collagen 1, relative lesion cross-sectional area, and histology scores for the analysis.

Key Findings

  • The study found that miR29a treatment reduced collagen 3 transcript levels at week 2, with no significant changes in collagen 1.
  • The relative lesion cross-sectional area was significantly lower in miR29a treated tendons compared to control tendons. This suggests that application of miR29a minimizes the injury area.
  • Additionally, histology scores were significantly better for miR29a-treated tendons compared to control tendons, implying better tendon condition after treatment.

Conclusion and Implications

  • Findings from this study support the mechanism of microRNA-mediated modulation of early pathophysiological events that facilitate tissue remodeling in the tendon after injury.
  • This signifies a strong proof of principle that a locally delivered miR29a therapy improves early tendon healing and could potentially be transformative for treating tendon injuries in human and equine athletes.

Cite This Article

APA
Watts AE, Millar NL, Platt J, Kitson SM, Akbar M, Rech R, Griffin J, Pool R, Hughes T, McInnes IB, Gilchrist DS. (2017). MicroRNA29a Treatment Improves Early Tendon Injury. Mol Ther, 25(10), 2415-2426. https://doi.org/10.1016/j.ymthe.2017.07.015

Publication

ISSN: 1525-0024
NlmUniqueID: 100890581
Country: United States
Language: English
Volume: 25
Issue: 10
Pages: 2415-2426
PII: S1525-0016(17)30356-8

Researcher Affiliations

Watts, Ashlee E
  • The Comparative Orthopedics and Regenerative Medicine Laboratory, Texas A&M University, College Station, TX 77843, USA.
Millar, Neal L
  • Institute of Infection, Immunity, and Inflammation, College of Medicine, Veterinary, and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK. Electronic address: neal.millar@glasgow.ac.uk.
Platt, Josh
  • The Comparative Orthopedics and Regenerative Medicine Laboratory, Texas A&M University, College Station, TX 77843, USA.
Kitson, Susan M
  • Institute of Infection, Immunity, and Inflammation, College of Medicine, Veterinary, and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.
Akbar, Moeed
  • Institute of Infection, Immunity, and Inflammation, College of Medicine, Veterinary, and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.
Rech, Raquel
  • The Comparative Orthopedics and Regenerative Medicine Laboratory, Texas A&M University, College Station, TX 77843, USA.
Griffin, Jay
  • The Comparative Orthopedics and Regenerative Medicine Laboratory, Texas A&M University, College Station, TX 77843, USA.
Pool, Roy
  • The Comparative Orthopedics and Regenerative Medicine Laboratory, Texas A&M University, College Station, TX 77843, USA.
Hughes, Tom
  • Liphook Equine Hospital, Forest Mere, Liphook GU30 7JG, UK.
McInnes, Iain B
  • Institute of Infection, Immunity, and Inflammation, College of Medicine, Veterinary, and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.
Gilchrist, Derek S
  • Institute of Infection, Immunity, and Inflammation, College of Medicine, Veterinary, and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK. Electronic address: derek.gilchrist@glasgow.ac.uk.

MeSH Terms

  • Animals
  • Collagen / genetics
  • Collagen / metabolism
  • Female
  • Horses
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Tendon Injuries / genetics
  • Tendon Injuries / metabolism
  • Tendon Injuries / therapy
  • Tendons / metabolism
  • Tendons / pathology

Grant Funding

  • MR/N005813/1 / Medical Research Council

References

This article includes 51 references
  1. Battery L, Maffulli N. Inflammation in overuse tendon injuries.. Sports Med Arthrosc Rev 2011 Sep;19(3):213-7.
    pubmed: 21822104doi: 10.1097/jsa.0b013e31820e6a92google scholar: lookup
  2. Birch HL. Tendon matrix composition and turnover in relation to functional requirements.. Int J Exp Pathol 2007 Aug;88(4):241-8.
  3. Dakin SG, Werling D, Hibbert A, Abayasekara DR, Young NJ, Smith RK, Dudhia J. Macrophage sub-populations and the lipoxin A4 receptor implicate active inflammation during equine tendon repair.. PLoS One 2012;7(2):e32333.
  4. Hyman J, Rodeo SA. Injury and repair of tendons and ligaments.. Phys Med Rehabil Clin N Am 2000 May;11(2):267-88, v.
    pubmed: 10810761
  5. Goodship AE. The pathophysiology of flexor tendon injury in the horse.. Equine Vet. Educ. 1993;5:23–29.
  6. Kasashima Y, Takahashi T, Smith RK, Goodship AE, Kuwano A, Ueno T, Hirano S. Prevalence of superficial digital flexor tendonitis and suspensory desmitis in Japanese Thoroughbred flat racehorses in 1999.. Equine Vet J 2004 May;36(4):346-50.
    pubmed: 15163043doi: 10.2746/0425164044890580google scholar: lookup
  7. Millar NL, Hueber AJ, Reilly JH, Xu Y, Fazzi UG, Murrell GA, McInnes IB. Inflammation is present in early human tendinopathy.. Am J Sports Med 2010 Oct;38(10):2085-91.
    pubmed: 20595553doi: 10.1177/0363546510372613google scholar: lookup
  8. Millar NL, Dean BJ, Dakin SG. Inflammation and the continuum model: time to acknowledge the molecular era of tendinopathy.. Br J Sports Med 2016 Dec;50(23):1486.
    pubmed: 27259752doi: 10.1136/bjsports-2016-096419google scholar: lookup
  9. Millar NL, Murrell GA, McInnes IB. Inflammatory mechanisms in tendinopathy - towards translation.. Nat Rev Rheumatol 2017 Jan 25;13(2):110-122.
    pubmed: 28119539doi: 10.1038/nrrheum.2016.213google scholar: lookup
  10. Dakin SG, Martinez FO, Yapp C, Wells G, Oppermann U, Dean BJ, Smith RD, Wheway K, Watkins B, Roche L, Carr AJ. Inflammation activation and resolution in human tendon disease.. Sci Transl Med 2015 Oct 28;7(311):311ra173.
  11. Behzad H, Sharma A, Mousavizadeh R, Lu A, Scott A. Mast cells exert pro-inflammatory effects of relevance to the pathophyisology of tendinopathy.. Arthritis Res Ther 2013;15(6):R184.
    pmc: PMC3978883pubmed: 24517261doi: 10.1186/ar4374google scholar: lookup
  12. John T, Lodka D, Kohl B, Ertel W, Jammrath J, Conrad C, Stoll C, Busch C, Schulze-Tanzil G. Effect of pro-inflammatory and immunoregulatory cytokines on human tenocytes.. J Orthop Res 2010 Aug;28(8):1071-7.
    pubmed: 20127972doi: 10.1002/jor.21079google scholar: lookup
  13. Dakin SG, Dudhia J, Smith RK. Science in brief: resolving tendon inflammation. A new perspective.. Equine Vet J 2013 Jul;45(4):398-400.
    pubmed: 23738877doi: 10.1111/evj.12030google scholar: lookup
  14. Dakin SG, Dudhia J, Werling NJ, Werling D, Abayasekara DR, Smith RK. Inflamm-aging and arachadonic acid metabolite differences with stage of tendon disease.. PLoS One 2012;7(11):e48978.
  15. Millar NL, Akbar M, Campbell AL, Reilly JH, Kerr SC, McLean M, Frleta-Gilchrist M, Fazzi UG, Leach WJ, Rooney BP, Crowe LA, Murrell GA, McInnes IB. IL-17A mediates inflammatory and tissue remodelling events in early human tendinopathy.. Sci Rep 2016 Jun 6;6:27149.
    pmc: PMC4893609pubmed: 27263531doi: 10.1038/srep27149google scholar: lookup
  16. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation.. Nat Rev Genet 2004 Jul;5(7):522-31.
    pubmed: 15211354doi: 10.1038/nrg1379google scholar: lookup
  17. Maurer B, Stanczyk J, Jüngel A, Akhmetshina A, Trenkmann M, Brock M, Kowal-Bielecka O, Gay RE, Michel BA, Distler JH, Gay S, Distler O. MicroRNA-29, a key regulator of collagen expression in systemic sclerosis.. Arthritis Rheum 2010 Jun;62(6):1733-43.
    pubmed: 20201077doi: 10.1002/art.27443google scholar: lookup
  18. Kurowska-Stolarska M, Alivernini S, Ballantine LE, Asquith DL, Millar NL, Gilchrist DS, Reilly J, Ierna M, Fraser AR, Stolarski B, McSharry C, Hueber AJ, Baxter D, Hunter J, Gay S, Liew FY, McInnes IB. MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis.. Proc Natl Acad Sci U S A 2011 Jul 5;108(27):11193-8.
    pmc: PMC3131377pubmed: 21690378doi: 10.1073/pnas.1019536108google scholar: lookup
  19. Bushati N, Cohen SM. microRNA functions.. Annu Rev Cell Dev Biol 2007;23:175-205.
  20. Bartel DP. MicroRNAs: target recognition and regulatory functions.. Cell 2009 Jan 23;136(2):215-33.
    pmc: PMC3794896pubmed: 19167326doi: 10.1016/j.cell.2009.01.002google scholar: lookup
  21. Zeng L, He X, Wang Y, Tang Y, Zheng C, Cai H, Liu J, Wang Y, Fu Y, Yang GY. MicroRNA-210 overexpression induces angiogenesis and neurogenesis in the normal adult mouse brain.. Gene Ther 2014 Jan;21(1):37-43.
    pubmed: 24152581doi: 10.1038/gt.2013.55google scholar: lookup
  22. Usman MA, Nakasa T, Shoji T, Kato T, Kawanishi Y, Hamanishi M, Kamei N, Ochi M. The effect of administration of double stranded MicroRNA-210 on acceleration of Achilles tendon healing in a rat model.. J Orthop Sci 2015 May;20(3):538-46.
    pubmed: 25753838doi: 10.1007/s00776-015-0709-5google scholar: lookup
  23. Chen CH, Zhou YL, Wu YF, Cao Y, Gao JS, Tang JB. Effectiveness of microRNA in Down-regulation of TGF-beta gene expression in digital flexor tendons of chickens: in vitro and in vivo study.. J Hand Surg Am 2009 Dec;34(10):1777-84.e1.
    pubmed: 19969188doi: 10.1016/j.jhsa.2009.07.015google scholar: lookup
  24. Chen Q, Lu H, Yang H. Chitosan inhibits fibroblasts growth in Achilles tendon via TGF-β1/Smad3 pathway by miR-29b.. Int J Clin Exp Pathol 2014;7(12):8462-70.
    pmc: PMC4313955pubmed: 25674210
  25. Millar NL, Gilchrist DS, Akbar M, Reilly JH, Kerr SC, Campbell AL, Murrell GAC, Liew FY, Kurowska-Stolarska M, McInnes IB. MicroRNA29a regulates IL-33-mediated tissue remodelling in tendon disease.. Nat Commun 2015 Apr 10;6:6774.
    pmc: PMC4403384pubmed: 25857925doi: 10.1038/ncomms7774google scholar: lookup
  26. Brown BD, Naldini L. Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications.. Nat Rev Genet 2009 Aug;10(8):578-85.
    pubmed: 19609263doi: 10.1038/nrg2628google scholar: lookup
  27. Abonnenc M, Nabeebaccus AA, Mayr U, Barallobre-Barreiro J, Dong X, Cuello F, Sur S, Drozdov I, Langley SR, Lu R, Stathopoulou K, Didangelos A, Yin X, Zimmermann WH, Shah AM, Zampetaki A, Mayr M. Extracellular matrix secretion by cardiac fibroblasts: role of microRNA-29b and microRNA-30c.. Circ Res 2013 Oct 25;113(10):1138-47.
    pubmed: 24006456doi: 10.1161/circresaha.113.302400google scholar: lookup
  28. Williams IF, McCullagh KG, Goodship AE, Silver IA. Studies on the pathogenesis of equine tendonitis following collagenase injury.. Res Vet Sci 1984 May;36(3):326-38.
    pubmed: 6087432
  29. Lake SP, Ansorge HL, Soslowsky LJ. Animal models of tendinopathy.. Disabil Rehabil 2008;30(20-22):1530-41.
    pubmed: 18608372doi: 10.1080/09638280701785460google scholar: lookup
  30. Sengupta S, den Boon JA, Chen IH, Newton MA, Stanhope SA, Cheng YJ, Chen CJ, Hildesheim A, Sugden B, Ahlquist P. MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins.. Proc Natl Acad Sci U S A 2008 Apr 15;105(15):5874-8.
    pmc: PMC2311339pubmed: 18390668doi: 10.1073/pnas.0801130105google scholar: lookup
  31. Qin W, Chung AC, Huang XR, Meng XM, Hui DS, Yu CM, Sung JJ, Lan HY. TGF-β/Smad3 signaling promotes renal fibrosis by inhibiting miR-29.. J Am Soc Nephrol 2011 Aug;22(8):1462-74.
    pmc: PMC3148701pubmed: 21784902doi: 10.1681/asn.2010121308google scholar: lookup
  32. Ciechomska M, O'Reilly S, Suwara M, Bogunia-Kubik K, van Laar JM. MiR-29a reduces TIMP-1 production by dermal fibroblasts via targeting TGF-β activated kinase 1 binding protein 1, implications for systemic sclerosis.. PLoS One 2014;9(12):e115596.
  33. Ganal E, Ho CP, Wilson KJ, Surowiec RK, Smith WS, Dornan GJ, Millett PJ. Quantitative MRI characterization of arthroscopically verified supraspinatus pathology: comparison of tendon tears, tendinosis and asymptomatic supraspinatus tendons with T2 mapping.. Knee Surg Sports Traumatol Arthrosc 2016 Jul;24(7):2216-24.
    pubmed: 25739912doi: 10.1007/s00167-015-3547-2google scholar: lookup
  34. Bangerter NK, Taylor MD, Tarbox GJ, Palmer AJ, Park DJ. Quantitative techniques for musculoskeletal MRI at 7 Tesla.. Quant Imaging Med Surg 2016 Dec;6(6):715-730.
    pmc: PMC5219959pubmed: 28090448doi: 10.21037/qims.2016.12.12google scholar: lookup
  35. van Schie HT, Bakker EM, Cherdchutham W, Jonker AM, van de Lest CH, van Weeren PR. Monitoring of the repair process of surgically created lesions in equine superficial digital flexor tendons by use of computerized ultrasonography.. Am J Vet Res 2009 Jan;70(1):37-48.
    pubmed: 19119947doi: 10.2460/ajvr.70.1.37google scholar: lookup
  36. Bosch G, Moleman M, Barneveld A, van Weeren PR, van Schie HT. The effect of platelet-rich plasma on the neovascularization of surgically created equine superficial digital flexor tendon lesions.. Scand J Med Sci Sports 2011 Aug;21(4):554-61.
  37. Bosch G, René van Weeren P, Barneveld A, van Schie HT. Computerised analysis of standardised ultrasonographic images to monitor the repair of surgically created core lesions in equine superficial digital flexor tendons following treatment with intratendinous platelet rich plasma or placebo.. Vet J 2011 Jan;187(1):92-8.
    pubmed: 19932036doi: 10.1016/j.tvjl.2009.10.014google scholar: lookup
  38. Garrett KS, Bramlage LR, Spike-Pierce DL, Cohen ND. Injection of platelet- and leukocyte-rich plasma at the junction of the proximal sesamoid bone and the suspensory ligament branch for treatment of yearling Thoroughbreds with proximal sesamoid bone inflammation and associated suspensory ligament branch desmitis.. J Am Vet Med Assoc 2013 Jul 1;243(1):120-5.
    pubmed: 23786200doi: 10.2460/javma.243.1.120google scholar: lookup
  39. de Vos RJ, Weir A, van Schie HT, Bierma-Zeinstra SM, Verhaar JA, Weinans H, Tol JL. Platelet-rich plasma injection for chronic Achilles tendinopathy: a randomized controlled trial.. JAMA 2010 Jan 13;303(2):144-9.
    pubmed: 20068208doi: 10.1001/jama.2009.1986google scholar: lookup
  40. Nixon AJ, Dahlgren LA, Haupt JL, Yeager AE, Ward DL. Effect of adipose-derived nucleated cell fractions on tendon repair in horses with collagenase-induced tendinitis.. Am J Vet Res 2008 Jul;69(7):928-37.
    pubmed: 18593247doi: 10.2460/ajvr.69.7.928google scholar: lookup
  41. Watts AE, Yeager AE, Kopyov OV, Nixon AJ. Fetal derived embryonic-like stem cells improve healing in a large animal flexor tendonitis model.. Stem Cell Res Ther 2011 Jan 27;2(1):4.
    pmc: PMC3092144pubmed: 21272343doi: 10.1186/scrt45google scholar: lookup
  42. Pacini S, Spinabella S, Trombi L, Fazzi R, Galimberti S, Dini F, Carlucci F, Petrini M. Suspension of bone marrow-derived undifferentiated mesenchymal stromal cells for repair of superficial digital flexor tendon in race horses.. Tissue Eng 2007 Dec;13(12):2949-55.
    pubmed: 17919069doi: 10.1089/ten.2007.0108google scholar: lookup
  43. Smith RK, Werling NJ, Dakin SG, Alam R, Goodship AE, Dudhia J. Beneficial effects of autologous bone marrow-derived mesenchymal stem cells in naturally occurring tendinopathy.. PLoS One 2013;8(9):e75697.
  44. Godwin EE, Young NJ, Dudhia J, Beamish IC, Smith RK. Implantation of bone marrow-derived mesenchymal stem cells demonstrates improved outcome in horses with overstrain injury of the superficial digital flexor tendon.. Equine Vet J 2012 Jan;44(1):25-32.
  45. Caplan AI, Correa D. The MSC: an injury drugstore.. Cell Stem Cell 2011 Jul 8;9(1):11-5.
    pmc: PMC3144500pubmed: 21726829doi: 10.1016/j.stem.2011.06.008google scholar: lookup
  46. Carvalho Ade M, Badial PR, Álvarez LE, Yamada AL, Borges AS, Deffune E, Hussni CA, Garcia Alves AL. Equine tendonitis therapy using mesenchymal stem cells and platelet concentrates: a randomized controlled trial.. Stem Cell Res Ther 2013 Jul 22;4(4):85.
    pmc: PMC3854756pubmed: 23876512doi: 10.1186/scrt236google scholar: lookup
  47. de Mattos Carvalho A, Garcia Alves AL, Galvão Gomes de Oliveira P, Cisneros Álvarez LE, Amorim RL, Hussni CA, Deffune E. Use of adipose tissue-derived mesenchymal stem cells for experimental tendinitis therapy in equines.. J. Equine Vet. Sci. 2011;31:26–34.
  48. Koch TG, Betts DH. Stem cell therapy for joint problems using the horse as a clinically relevant animal model.. Expert Opin Biol Ther 2007 Nov;7(11):1621-6.
    pubmed: 17961087doi: 10.1517/14712598.7.11.1621google scholar: lookup
  49. Abate M, Silbernagel KG, Siljeholm C, Di Iorio A, De Amicis D, Salini V, Werner S, Paganelli R. Pathogenesis of tendinopathies: inflammation or degeneration?. Arthritis Res Ther 2009;11(3):235.
    pmc: PMC2714139pubmed: 19591655doi: 10.1186/ar2723google scholar: lookup
  50. Dowling BA, Dart AJ, Hodgson DR, Smith RK. Superficial digital flexor tendonitis in the horse.. Equine Vet J 2000 Sep;32(5):369-78.
    pubmed: 11037257doi: 10.2746/042516400777591138google scholar: lookup
  51. Watts AE, Nixon AJ, Yeager AE, Mohammed HO. A collagenase gel/physical defect model for controlled induction of superficial digital flexor tendonitis.. Equine Vet J 2012 Sep;44(5):576-86.

Citations

This article has been cited 29 times.
  1. Morya VK, Lee HW, Park CW, Park CW, Hyun JT, Noh KC. Computational Analysis of miR-140 and miR-135 as Potential Targets to Develop Combinatorial Therapeutics for Degenerative Tendinopathy.. Clin Orthop Surg 2023 Jun;15(3):463-476.
    doi: 10.4055/cios22237pubmed: 37274502google scholar: lookup
  2. Lyu K, Liu X, Liu T, Lu J, Jiang L, Chen Y, Long L, Wang X, Shi H, Wang F, Li S. miRNAs contributing to the repair of tendon injury.. Cell Tissue Res 2023 Aug;393(2):201-215.
    doi: 10.1007/s00441-023-03780-8pubmed: 37249708google scholar: lookup
  3. Peniche Silva CJ, De La Vega RE, Panos J, Joris V, Evans CH, Balmayor ER, van Griensven M. MiRNAs as Potential Regulators of Enthesis Healing: Findings in a Rodent Injury Model.. Int J Mol Sci 2023 May 10;24(10).
    doi: 10.3390/ijms24108556pubmed: 37239902google scholar: lookup
  4. Xiang DD, Liu JT, Zhong ZB, Xiong Y, Kong HY, Yu HJ, Peng T, Huang JQ. MicroRNA-29a-3p Prevents Drug-Induced Acute Liver Failure through Inflammation-Related Pyroptosis Inhibition.. Curr Med Sci 2023 Jun;43(3):456-468.
    doi: 10.1007/s11596-023-2734-5pubmed: 37115401google scholar: lookup
  5. Wawrose RA, Oyekan AA, Tang YM, Chen SR, Chen J, Couch BK, Wang D, Alexander PG, Sowa GA, Vo NV, Lee JY. MicroRNA-29a: a novel target for non-operative management of symptomatic lumbar spinal stenosis.. Eur Spine J 2023 Apr 12;.
    doi: 10.1007/s00586-023-07671-ypubmed: 37046075google scholar: lookup
  6. Mok TN, He Q, Zhang X, Sin TH, Wang H, Hou H, Pan J, Zheng X, Zha Z, Li J. Effects of 6-Hydroxykaempferol: A Potential Natural Product for Amelioration of Tendon Impairment.. Front Pharmacol 2022;13:919104.
    doi: 10.3389/fphar.2022.919104pubmed: 35935848google scholar: lookup
  7. Wang HN, Rong X, Yang LM, Hua WZ, Ni GX. Advances in Stem Cell Therapies for Rotator Cuff Injuries.. Front Bioeng Biotechnol 2022;10:866195.
    doi: 10.3389/fbioe.2022.866195pubmed: 35694228google scholar: lookup
  8. Lyu K, Liu T, Chen Y, Lu J, Jiang L, Liu X, Liu X, Li Y, Li S. A "cell-free treatment" for tendon injuries: adipose stem cell-derived exosomes.. Eur J Med Res 2022 May 28;27(1):75.
    doi: 10.1186/s40001-022-00707-xpubmed: 35643543google scholar: lookup
  9. Freedman BR, Kuttler A, Beckmann N, Nam S, Kent D, Schuleit M, Ramazani F, Accart N, Rock A, Li J, Kurz M, Fisch A, Ullrich T, Hast MW, Tinguely Y, Weber E, Mooney DJ. Enhanced tendon healing by a tough hydrogel with an adhesive side and high drug-loading capacity.. Nat Biomed Eng 2022 Oct;6(10):1167-1179.
    doi: 10.1038/s41551-021-00810-0pubmed: 34980903google scholar: lookup
  10. Marr N, Meeson R, Kelly EF, Fang Y, Peffers MJ, Pitsillides AA, Dudhia J, Thorpe CT. CD146 Delineates an Interfascicular Cell Sub-Population in Tendon That Is Recruited during Injury through Its Ligand Laminin-α4.. Int J Mol Sci 2021 Sep 8;22(18).
    doi: 10.3390/ijms22189729pubmed: 34575887google scholar: lookup
  11. Liu Q, Zhu Y, Zhu W, Zhang G, Yang YP, Zhao C. The role of MicroRNAs in tendon injury, repair, and related tissue engineering.. Biomaterials 2021 Oct;277:121083.
  12. Gaesser AM, Underwood C, Linardi RL, Even KM, Reef VB, Shetye SS, Mauck RL, King WJ, Engiles JB, Ortved KF. Evaluation of Autologous Protein Solution Injection for Treatment of Superficial Digital Flexor Tendonitis in an Equine Model.. Front Vet Sci 2021;8:697551.
    doi: 10.3389/fvets.2021.697551pubmed: 34291103google scholar: lookup
  13. Ding L, Wang M, Qin S, Xu L. The Roles of MicroRNAs in Tendon Healing and Regeneration.. Front Cell Dev Biol 2021;9:687117.
    doi: 10.3389/fcell.2021.687117pubmed: 34277629google scholar: lookup
  14. Yao Z, Li J, Xiong H, Cui H, Ning J, Wang S, Ouyang X, Qian Y, Fan C. MicroRNA engineered umbilical cord stem cell-derived exosomes direct tendon regeneration by mTOR signaling.. J Nanobiotechnology 2021 Jun 5;19(1):169.
    doi: 10.1186/s12951-021-00906-4pubmed: 34090456google scholar: lookup
  15. Lee S, Baker ME, Clinton M, Taylor SE. Use of Omics Data in Fracture Prediction; a Scoping and Systematic Review in Horses and Humans.. Animals (Basel) 2021 Mar 30;11(4).
    doi: 10.3390/ani11040959pubmed: 33808497google scholar: lookup
  16. Kang S, Ye Y, Xia G, Liu HB. Coronary artery disease: differential expression of ceRNAs and interaction analyses.. Ann Transl Med 2021 Feb;9(3):229.
    doi: 10.21037/atm-20-3487pubmed: 33708856google scholar: lookup
  17. Horita M, Farquharson C, Stephen LA. The role of miR-29 family in disease.. J Cell Biochem 2021 Jul;122(7):696-715.
    doi: 10.1002/jcb.29896pubmed: 33529442google scholar: lookup
  18. Zamboulis DE, Thorpe CT, Ashraf Kharaz Y, Birch HL, Screen HR, Clegg PD. Postnatal mechanical loading drives adaptation of tissues primarily through modulation of the non-collagenous matrix.. Elife 2020 Oct 16;9.
    doi: 10.7554/eLife.58075pubmed: 33063662google scholar: lookup
  19. Ragni E, Perucca Orfei C, Silini AR, Colombini A, Viganò M, Parolini O, de Girolamo L. miRNA Reference Genes in Extracellular Vesicles Released from Amniotic Membrane-Derived Mesenchymal Stromal Cells.. Pharmaceutics 2020 Apr 11;12(4).
    doi: 10.3390/pharmaceutics12040347pubmed: 32290510google scholar: lookup
  20. Liao X, Falcon ND, Mohammed AA, Paterson YZ, Mayes AG, Guest DJ, Saeed A. Synthesis and Formulation of Four-Arm PolyDMAEA-siRNA Polyplex for Transient Downregulation of Collagen Type III Gene Expression in TGF-β1 Stimulated Tenocyte Culture.. ACS Omega 2020 Jan 28;5(3):1496-1505.
    doi: 10.1021/acsomega.9b03216pubmed: 32010823google scholar: lookup
  21. Ko JY, Lian WS, Tsai TC, Chen YS, Hsieh CK, Kuo CW, Wang FS. MicroRNA-29a Mitigates Subacromial Bursa Fibrosis in Rotator Cuff Lesion with Shoulder Stiffness.. Int J Mol Sci 2019 Nov 15;20(22).
    doi: 10.3390/ijms20225742pubmed: 31731750google scholar: lookup
  22. Plachel F, Heuberer P, Gehwolf R, Frank J, Tempfer H, Lehner C, Weissenbacher N, Wagner A, Weigl M, Moroder P, Hackl M, Traweger A. MicroRNA Profiling Reveals Distinct Signatures in Degenerative Rotator Cuff Pathologies.. J Orthop Res 2020 Jan;38(1):202-211.
    doi: 10.1002/jor.24473pubmed: 31520478google scholar: lookup
  23. Liu Y, Feng L, Xu J, Yang Z, Wu T, Zhang J, Shi L, Zhu D, Zhang J, Li G. MiR-378a suppresses tenogenic differentiation and tendon repair by targeting at TGF-β2.. Stem Cell Res Ther 2019 Mar 29;10(1):108.
    doi: 10.1186/s13287-019-1216-ypubmed: 30922407google scholar: lookup
  24. Freedman BR, Mooney DJ. Biomaterials to Mimic and Heal Connective Tissues.. Adv Mater 2019 May;31(19):e1806695.
    doi: 10.1002/adma.201806695pubmed: 30908806google scholar: lookup
  25. Cui H, He Y, Chen S, Zhang D, Yu Y, Fan C. Macrophage-Derived miRNA-Containing Exosomes Induce Peritendinous Fibrosis after Tendon Injury through the miR-21-5p/Smad7 Pathway.. Mol Ther Nucleic Acids 2019 Mar 1;14:114-130.
    doi: 10.1016/j.omtn.2018.11.006pubmed: 30594070google scholar: lookup
  26. Suter-Dick L, Mauch L, Ramp D, Caj M, Vormann MK, Hutter S, Lanz HL, Vriend J, Masereeuw R, Wilmer MJ. Combining Extracellular miRNA Determination with Microfluidic 3D Cell Cultures for the Assessment of Nephrotoxicity: a Proof of Concept Study.. AAPS J 2018 Jul 23;20(5):86.
    doi: 10.1208/s12248-018-0245-2pubmed: 30039346google scholar: lookup
  27. Alivernini S, Gremese E, McSharry C, Tolusso B, Ferraccioli G, McInnes IB, Kurowska-Stolarska M. MicroRNA-155-at the Critical Interface of Innate and Adaptive Immunity in Arthritis.. Front Immunol 2017;8:1932.
    doi: 10.3389/fimmu.2017.01932pubmed: 29354135google scholar: lookup
  28. Alivernini S, Tolusso B, Ferraccioli G, Gremese E, Kurowska-Stolarska M, McInnes IB. Driving chronicity in rheumatoid arthritis: perpetuating role of myeloid cells.. Clin Exp Immunol 2018 Jul;193(1):13-23.
    doi: 10.1111/cei.13098pubmed: 29315512google scholar: lookup
  29. Dakin SG. MicroRNA Replacement: A New Era of Molecular Therapy for Tendon Disorders?. Mol Ther 2017 Oct 4;25(10):2243-2244.
    doi: 10.1016/j.ymthe.2017.09.004pubmed: 28939087google scholar: lookup