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Gene therapy2002; 9(1); 12-20; doi: 10.1038/sj.gt.3301608

Treatment of experimental equine osteoarthritis by in vivo delivery of the equine interleukin-1 receptor antagonist gene.

Abstract: Osteoarthritis in horses and in humans is a significant social and economic problem and continued research and improvements in therapy are needed. Because horses have naturally occurring osteoarthritis, which is similar to that of humans, the horse was chosen as a species with which to investigate gene transfer as a potential therapeutic modality for the clinical treatment of osteoarthritis. Using an established model of equine osteoarthritis that mimics clinical osteoarthritis, the therapeutic effects resulting from intra-articular overexpression of the equine interleukin-1 receptor antagonist gene through adenoviral-mediated gene transfer were investigated. In vivo delivery of the equine IL-IRa gene led to elevated intra-articular expression of interleukin-1 receptor antagonist for approximately 28 days, resulting in significant improvement in clinical parameters of pain and disease activity, preservation of articular cartilage, and beneficial effects on the histologic parameters of synovial membrane and articular cartilage. Based on these findings, gene transfer of interleukin-1 receptor antagonist is an attractive treatment modality for the equine patient and also offers future promise for human patients with osteoarthritis.
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Publication Date: 2002-02-19 PubMed ID: 11850718DOI: 10.1038/sj.gt.3301608Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

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.

The study explores the potential of gene therapy in treating equine osteoarthritis by delivering the horse variant of the interleukin-1 receptor antagonist (IL-1Ra) gene. The experiment led to a significant improvement in pain and disease activity, preservation of cartilage, and beneficial effects on the synovial membrane and articular cartilage, upholding the promise for future application to human osteoarthritis treatment.

Objective of the Research

  • The primary goal of this research is to investigate the therapeutic potential of gene transfer for the treatment of osteoarthritis in horses. Given similarities between equine and human osteoarthritis, the horse was chosen as an ideal model to test this therapy potentially for future application on humans.

Methodology

  • Researchers used an established model of equine osteoarthritis to study the therapeutic effects of gene transfer.
  • The gene in question was the equine interleukin-1 receptor antagonist gene (IL-1Ra), transferred using an adenoviral vector. This gene and its product play a significant role in the regulation of inflammation, a critical component of osteoarthritis pathology.
  • The gene was delivered in vivo (“inside the body”) directly into the arthritic joint, leading to its overexpression in the local environment.

Results and Findings

  • Intra-articular overexpression of the equine IL-1Ra gene led to elevated local levels of the interleukin-1 receptor antagonist for about 28 days.
  • Most importantly, this increased gene expression resulted in significant improvements in pain and disease activity, effectively slowing the progression of the osteoarthritic condition.
  • Additionally, beneficial effects were observed in the synovial membrane and articular cartilage, tissues often affected in osteoarthritis. This suggests a level of ‘disease-modifying’ impact, beyond just symptom relief.

Implications and Future Promise

  • The results propose gene transfer of interleukin-1 receptor antagonist as an attractive treatment modality for equine patients, with a prospect for application in the treatment for human osteoarthritis.
  • Present day treatments for osteoarthritis often target symptom relief rather than altering disease progression, and thus this research offers significant promise for future improvement in osteoarthritis therapy.

Cite This Article

APA
Frisbie DD, Ghivizzani SC, Robbins PD, Evans CH, McIlwraith CW. (2002). Treatment of experimental equine osteoarthritis by in vivo delivery of the equine interleukin-1 receptor antagonist gene. Gene Ther, 9(1), 12-20. https://doi.org/10.1038/sj.gt.3301608

Publication

Gene therapy
ISSN: 0969-7128
NlmUniqueID: 9421525
Country: England
Language: English
Volume: 9
Issue: 1
Pages: 12-20

Researcher Affiliations

Frisbie, D D
  • Equine Orthopaedic Research Laboratory, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Ghivizzani, S C
    Robbins, P D
      Evans, C H
        McIlwraith, C W

          MeSH Terms

          • Adenoviridae / genetics
          • Analysis of Variance
          • Animals
          • Gene Expression
          • Genetic Therapy / methods
          • Genetic Vectors / administration & dosage
          • Horse Diseases / therapy
          • Horses
          • Injections, Intra-Articular
          • Models, Animal
          • Osteoarthritis / therapy
          • Osteoarthritis / veterinary
          • Receptors, Interleukin-1 / antagonists & inhibitors
          • Transduction, Genetic / methods

          Citations

          This article has been cited 115 times.
          1. Thampi P, Seabaugh KA, Pezzanite LM, Chu CR, Phillips JN, Grieger JC, McIlwraith CW, Samulski RJ, Goodrich LR. A pilot study to determine the optimal dose of scAAVIL-1ra in a large animal model of post-traumatic osteoarthritis. Gene Ther 2023 Sep 11;.
            doi: 10.1038/s41434-023-00420-2pubmed: 37696981google scholar: lookup
          2. Uebelhoer M, Lambert C, Grisart J, Guse K, Plutizki S, Henrotin Y. Interleukins, growth factors, and transcription factors are key targets for gene therapy in osteoarthritis: A scoping review. Front Med (Lausanne) 2023;10:1148623.
            doi: 10.3389/fmed.2023.1148623pubmed: 37077668google scholar: lookup
          3. Panizzi L, Dittmer KE, Vignes M, Doucet JS, Gedye K, Waterland MR, Rogers CW, Sano H, McIlwraith CW, Riley CB. Plasma and Synovial Fluid Cell-Free DNA Concentrations Following Induction of Osteoarthritis in Horses. Animals (Basel) 2023 Mar 14;13(6).
            doi: 10.3390/ani13061053pubmed: 36978592google scholar: lookup
          4. Mayet A, Zablotski Y, Roth SP, Brehm W, Troillet A. Systematic review and meta-analysis of positive long-term effects after intra-articular administration of orthobiologic therapeutics in horses with naturally occurring osteoarthritis. Front Vet Sci 2023;10:1125695.
            doi: 10.3389/fvets.2023.1125695pubmed: 36908512google scholar: lookup
          5. Evans CH, Ghivizzani SC, Robbins PD. Osteoarthritis gene therapy in 2022. Curr Opin Rheumatol 2023 Jan 1;35(1):37-43.
            doi: 10.1097/BOR.0000000000000918pubmed: 36508307google scholar: lookup
          6. Clarke EJ, Johnson E, Caamaño Gutierrez E, Andersen C, Berg LC, Jenkins RE, Lindegaard C, Uvebrant K, Lundgren-Åkerlund E, Turlo A, James V, Jacobsen S, Peffers MJ. Temporal extracellular vesicle protein changes following intraarticular treatment with integrin α10β1-selected mesenchymal stem cells in equine osteoarthritis. Front Vet Sci 2022;9:1057667.
            doi: 10.3389/fvets.2022.1057667pubmed: 36504839google scholar: lookup
          7. Panizzi L, Vignes M, Dittmer KE, Waterland MR, Rogers CW, Sano H, McIlwraith CW, Pemberton S, Owen M, Riley CB. Infrared spectroscopy of serum fails to identify early biomarker changes in an equine model of traumatic osteoarthritis. Osteoarthr Cartil Open 2022 Dec;4(4):100297.
            doi: 10.1016/j.ocarto.2022.100297pubmed: 36474792google scholar: lookup
          8. Thampi P, Samulski RJ, Grieger JC, Phillips JN, McIlwraith CW, Goodrich LR. Gene therapy approaches for equine osteoarthritis. Front Vet Sci 2022;9:962898.
            doi: 10.3389/fvets.2022.962898pubmed: 36246316google scholar: lookup
          9. Banstola A, Reynolds JNJ. The Sheep as a Large Animal Model for the Investigation and Treatment of Human Disorders. Biology (Basel) 2022 Aug 23;11(9).
            doi: 10.3390/biology11091251pubmed: 36138730google scholar: lookup
          10. Garbin LC, McIlwraith CW, Frisbie DD. Use of allogeneic freeze-dried conditioned serum for the prevention of degradation in cartilage exposed to IL-1ß. BMC Vet Res 2022 Jul 11;18(1):265.
            doi: 10.1186/s12917-022-03227-2pubmed: 35820849google scholar: lookup
          11. Andersen C, Jacobsen S, Walters M, Lindegaard C. A detailed macroscopic scoring system for experimental post-traumatic Osteoarthritis in the equine middle carpal joint. BMC Res Notes 2022 Jun 27;15(1):226.
            doi: 10.1186/s13104-022-06116-xpubmed: 35761416google scholar: lookup
          12. Mohammadi A, Te Moller NCR, Ebrahimi M, Plomp S, Brommer H, van Weeren PR, Mäkelä JTA, Töyräs J, Korhonen RK. Site- and Zone-Dependent Changes in Proteoglycan Content and Biomechanical Properties of Bluntly and Sharply Grooved Equine Articular Cartilage. Ann Biomed Eng 2022 Dec;50(12):1787-1797.
            doi: 10.1007/s10439-022-02991-4pubmed: 35754073google scholar: lookup
          13. Seabaugh KA, Barrett MF, Rao S, McIlwraith CW, Frisbie DD. Examining the Effects of the Oral Supplement Biota orientalis in the Osteochondral Fragment-Exercise Model of Osteoarthritis in the Horse. Front Vet Sci 2022;9:858391.
            doi: 10.3389/fvets.2022.858391pubmed: 35720848google scholar: lookup
          14. Yamada ALM, do Prado Vendruscolo C, Marsiglia MF, Sotelo EDP, Agreste FR, Seidel SRT, Fülber J, Baccarin RYA, da Silva LCLC. Effects of oral treatment with chondroitin sulfate and glucosamine in an experimental model of metacarpophalangeal osteoarthritis in horses. BMC Vet Res 2022 Jun 9;18(1):215.
            doi: 10.1186/s12917-022-03323-3pubmed: 35681208google scholar: lookup
          15. Löfgren M, Ekman S, Ekholm J, Engström M, Fjordbakk CT, Svala E, Holm Forsström K, Lindahl A, Skiöldebrand E. Conditioned serum in vitro treatment of chondrocyte pellets and osteoarthritic explants. Equine Vet J 2023 Mar;55(2):325-335.
            doi: 10.1111/evj.13582pubmed: 35514185google scholar: lookup
          16. Timmons RB, Sugaya K, Bane LD. Homologous Use of Allogeneic Umbilical Cord Tissue to Reduce Knee Pain and Improve Knee Function. Life (Basel) 2022 Feb 9;12(2).
            doi: 10.3390/life12020260pubmed: 35207547google scholar: lookup
          17. Senter R, Boyce R, Repic M, Martin EW, Chabicovsky M, Langevin-Carpentier G, Bédard A, Bodick N. Efficacy and Safety of FX201, a Novel Intra-Articular IL-1Ra Gene Therapy for Osteoarthritis Treatment, in a Rat Model. Hum Gene Ther 2022 May;33(9-10):541-549.
            doi: 10.1089/hum.2021.131pubmed: 34963343google scholar: lookup
          18. Hale J, Hughes K, Hall S, Labens R. Effects of Production Method and Repeated Freeze Thaw Cycles on Cytokine Concentrations and Microbial Contamination in Equine Autologous Conditioned Serum. Front Vet Sci 2021;8:759828.
            doi: 10.3389/fvets.2021.759828pubmed: 34901249google scholar: lookup
          19. Ribitsch I, Oreff GL, Jenner F. Regenerative Medicine for Equine Musculoskeletal Diseases. Animals (Basel) 2021 Jan 19;11(1).
            doi: 10.3390/ani11010234pubmed: 33477808google scholar: lookup
          20. McCoy AM, Kemper AM, Boyce MK, Brown MP, Trumble TN. Differential gene expression analysis reveals pathways important in early post-traumatic osteoarthritis in an equine model. BMC Genomics 2020 Nov 30;21(1):843.
            doi: 10.1186/s12864-020-07228-zpubmed: 33256611google scholar: lookup
          21. Pritchard A, Nielsen BD, Robison C, Manfredi JM. Low dietary silicon supplementation may not affect bone and cartilage in mature, sedentary horses. J Anim Sci 2020 Dec 1;98(12).
            doi: 10.1093/jas/skaa377pubmed: 33216909google scholar: lookup
          22. Lian C, Tao T, Su P, Liao Z, Wang X, Lei Y, Zhao P, Liu L. Targeting miR-18a sensitizes chondrocytes to anticytokine therapy to prevent osteoarthritis progression. Cell Death Dis 2020 Nov 3;11(11):947.
            doi: 10.1038/s41419-020-03155-9pubmed: 33144571google scholar: lookup
          23. Mead OG, Mead LP. Intra-Articular Injection of Amniotic Membrane and Umbilical Cord Particulate for the Management of Moderate to Severe Knee Osteoarthritis. Orthop Res Rev 2020;12:161-170.
            doi: 10.2147/ORR.S272980pubmed: 33116955google scholar: lookup
          24. Maki CB, Beck A, Wallis CCC, Choo J, Ramos T, Tong R, Borjesson DL, Izadyar F. Intra-articular Administration of Allogeneic Adipose Derived MSCs Reduces Pain and Lameness in Dogs With Hip Osteoarthritis: A Double Blinded, Randomized, Placebo Controlled Pilot Study. Front Vet Sci 2020;7:570.
            doi: 10.3389/fvets.2020.00570pubmed: 33110913google scholar: lookup
          25. Edwards KL, Miller MA, Siegal-Willott J, Brown JL. Serum Health Biomarkers in African and Asian Elephants: Value Ranges and Clinical Values Indicative of the Immune Response. Animals (Basel) 2020 Sep 27;10(10).
            doi: 10.3390/ani10101756pubmed: 32992555google scholar: lookup
          26. Marques-Smith P, Kallerud AS, Johansen GM, Boysen P, Jacobsen AM, Reitan KM, Henriksen MM, Löfgren M, Fjordbakk CT. Is clinical effect of autologous conditioned serum in spontaneously occurring equine articular lameness related to ACS cytokine profile?. BMC Vet Res 2020 Jun 8;16(1):181.
            doi: 10.1186/s12917-020-02391-7pubmed: 32513154google scholar: lookup
          27. Lacitignola L, Imperante A, Staffieri F, De Siena R, De Luca P, Muci A, Crovace A. Assessment of Intra- and Inter-observer Measurement Variability in a Radiographic Metacarpophalangeal Joint Osteophytosis Scoring System for the Horse. Vet Sci 2020 Apr 6;7(2).
            doi: 10.3390/vetsci7020039pubmed: 32268589google scholar: lookup
          28. Ghouri A, Conaghan PG. Prospects for Therapies in Osteoarthritis. Calcif Tissue Int 2021 Sep;109(3):339-350.
            doi: 10.1007/s00223-020-00672-9pubmed: 32055890google scholar: lookup
          29. Colbath AC, Dow SW, Hopkins LS, Phillips JN, McIlwraith CW, Goodrich LR. Single and repeated intra-articular injections in the tarsocrural joint with allogeneic and autologous equine bone marrow-derived mesenchymal stem cells are safe, but did not reduce acute inflammation in an experimental interleukin-1β model of synovitis. Equine Vet J 2020 Jul;52(4):601-612.
            doi: 10.1111/evj.13222pubmed: 31821594google scholar: lookup
          30. Ghouri A, Conaghan PG. Update on novel pharmacological therapies for osteoarthritis. Ther Adv Musculoskelet Dis 2019;11:1759720X19864492.
            doi: 10.1177/1759720X19864492pubmed: 31384314google scholar: lookup
          31. Niemelä TM, Tulamo RM, Carmona JU, López C. Evaluation of the effect of experimentally induced cartilage defect and intra-articular hyaluronan on synovial fluid biomarkers in intercarpal joints of horses. Acta Vet Scand 2019 May 30;61(1):24.
            doi: 10.1186/s13028-019-0460-6pubmed: 31146775google scholar: lookup
          32. Patel JM, Saleh KS, Burdick JA, Mauck RL. Bioactive factors for cartilage repair and regeneration: Improving delivery, retention, and activity. Acta Biomater 2019 Jul 15;93:222-238.
            doi: 10.1016/j.actbio.2019.01.061pubmed: 30711660google scholar: lookup
          33. Colbath AC, Dow SW, Hopkins LS, Phillips JN, McIlwraith CW, Goodrich LR. Induction of Synovitis Using Interleukin-1 Beta: Are There Differences in the Response of Middle Carpal Joint Compared to the Tibiotarsal Joint?. Front Vet Sci 2018;5:208.
            doi: 10.3389/fvets.2018.00208pubmed: 30234134google scholar: lookup
          34. Evans C. Editorial: Arthritis Gene Therapy Using Interleukin-1 Receptor Antagonist. Arthritis Rheumatol 2018 Nov;70(11):1699-1701.
            doi: 10.1002/art.40675pubmed: 30035385google scholar: lookup
          35. Wu F, Xu J, Zhu Z. Protective Effect of Tetrandrine in a Rabbit Model of Osteoarthritis. Arch Rheumatol 2018 Mar;33(1):80-84.
            doi: 10.5606/ArchRheumatol.2018.6387pubmed: 29901017google scholar: lookup
          36. Watson Levings RS, Broome TA, Smith AD, Rice BL, Gibbs EP, Myara DA, Hyddmark EV, Nasri E, Zarezadeh A, Levings PP, Lu Y, White ME, Dacanay EA, Foremny GB, Evans CH, Morton AJ, Winter M, Dark MJ, Nickerson DM, Colahan PT, Ghivizzani SC. Gene Therapy for Osteoarthritis: Pharmacokinetics of Intra-Articular Self-Complementary Adeno-Associated Virus Interleukin-1 Receptor Antagonist Delivery in an Equine Model. Hum Gene Ther Clin Dev 2018 Jun;29(2):90-100.
            doi: 10.1089/humc.2017.142pubmed: 29869540google scholar: lookup
          37. Watson Levings RS, Smith AD, Broome TA, Rice BL, Gibbs EP, Myara DA, Hyddmark EV, Nasri E, Zarezadeh A, Levings PP, Lu Y, White ME, Dacanay EA, Foremny GB, Evans CH, Morton AJ, Winter M, Dark MJ, Nickerson DM, Colahan PT, Ghivizzani SC. Self-Complementary Adeno-Associated Virus-Mediated Interleukin-1 Receptor Antagonist Gene Delivery for the Treatment of Osteoarthritis: Test of Efficacy in an Equine Model. Hum Gene Ther Clin Dev 2018 Jun;29(2):101-112.
            doi: 10.1089/humc.2017.143pubmed: 29869535google scholar: lookup
          38. Gabner S, Ertl R, Velde K, Renner M, Jenner F, Egerbacher M, Hlavaty J. Cytokine-induced interleukin-1 receptor antagonist protein expression in genetically engineered equine mesenchymal stem cells for osteoarthritis treatment. J Gene Med 2018 May;20(5):e3021.
            doi: 10.1002/jgm.3021pubmed: 29608232google scholar: lookup
          39. Evans CH, Ghivizzani SC, Robbins PD. Gene Delivery to Joints by Intra-Articular Injection. Hum Gene Ther 2018 Jan;29(1):2-14.
            doi: 10.1089/hum.2017.181pubmed: 29160173google scholar: lookup
          40. Rey-Rico A, Venkatesan JK, Schmitt G, Concheiro A, Madry H, Alvarez-Lorenzo C, Cucchiarini M. rAAV-mediated overexpression of TGF-β via vector delivery in polymeric micelles stimulates the biological and reparative activities of human articular chondrocytes in vitro and in a human osteochondral defect model. Int J Nanomedicine 2017;12:6985-6996.
            doi: 10.2147/IJN.S144579pubmed: 29033566google scholar: lookup
          41. Wehling P, Evans C, Wehling J, Maixner W. Effectiveness of intra-articular therapies in osteoarthritis: a literature review. Ther Adv Musculoskelet Dis 2017 Aug;9(8):183-196.
            doi: 10.1177/1759720X17712695pubmed: 28835778google scholar: lookup
          42. Nasi S, Ea HK, So A, Busso N. Revisiting the Role of Interleukin-1 Pathway in Osteoarthritis: Interleukin-1α and -1β, and NLRP3 Inflammasome Are Not Involved in the Pathological Features of the Murine Menisectomy Model of Osteoarthritis. Front Pharmacol 2017;8:282.
            doi: 10.3389/fphar.2017.00282pubmed: 28659793google scholar: lookup
          43. Punzi L, Galozzi P, Luisetto R, Favero M, Ramonda R, Oliviero F, Scanu A. Post-traumatic arthritis: overview on pathogenic mechanisms and role of inflammation. RMD Open 2016;2(2):e000279.
            doi: 10.1136/rmdopen-2016-000279pubmed: 27651925google scholar: lookup
          44. Rey-Rico A, Madry H, Cucchiarini M. Hydrogel-Based Controlled Delivery Systems for Articular Cartilage Repair. Biomed Res Int 2016;2016:1215263.
            doi: 10.1155/2016/1215263pubmed: 27642587google scholar: lookup
          45. Reesink HL, Watts AE, Mohammed HO, Jay GD, Nixon AJ. Lubricin/proteoglycan 4 increases in both experimental and naturally occurring equine osteoarthritis. Osteoarthritis Cartilage 2017 Jan;25(1):128-137.
            doi: 10.1016/j.joca.2016.07.021pubmed: 27498214google scholar: lookup
          46. Ortved KF, Austin BS, Scimeca MS, Nixon AJ. RNA Interference Mediated Interleukin-1β Silencing in Inflamed Chondrocytes Decreases Target and Downstream Catabolic Responses. Arthritis 2016;2016:3484961.
            doi: 10.1155/2016/3484961pubmed: 27073697google scholar: lookup
          47. Wang G, Evans CH, Benson JM, Hutt JA, Seagrave J, Wilder JA, Grieger JC, Samulski RJ, Terse PS. Safety and biodistribution assessment of sc-rAAV2.5IL-1Ra administered via intra-articular injection in a mono-iodoacetate-induced osteoarthritis rat model. Mol Ther Methods Clin Dev 2016;3:15052.
            doi: 10.1038/mtm.2015.52pubmed: 26817025google scholar: lookup
          48. Lieberthal J, Sambamurthy N, Scanzello CR. Inflammation in joint injury and post-traumatic osteoarthritis. Osteoarthritis Cartilage 2015 Nov;23(11):1825-34.
            doi: 10.1016/j.joca.2015.08.015pubmed: 26521728google scholar: lookup
          49. Agarwal R, Volkmer TM, Wang P, Lee LA, Wang Q, García AJ. Synthesis of self-assembled IL-1Ra-presenting nanoparticles for the treatment of osteoarthritis. J Biomed Mater Res A 2016 Mar;104(3):595-599.
            doi: 10.1002/jbm.a.35601pubmed: 26507256google scholar: lookup
          50. Gopinath C, Nathar TJ, Ghosh A, Hickstein DD, Nelson EJR. Contemporary Animal Models For Human Gene Therapy Applications. Curr Gene Ther 2015;15(6):531-40.
            doi: 10.2174/1566523215666150929110424pubmed: 26415576google scholar: lookup
          51. Malda J, McIlwraith CW. Current Trends in Cartilage Science: An Impression from the ICRS World Conference 2012. Cartilage 2013 Oct;4(4):273-80.
            doi: 10.1177/1947603513479606pubmed: 26069672google scholar: lookup
          52. Chubinskaya S, Wimmer MA. Key Pathways to Prevent Posttraumatic Arthritis for Future Molecule-Based Therapy. Cartilage 2013 Jul;4(3 Suppl):13S-21S.
            doi: 10.1177/1947603513487457pubmed: 26069661google scholar: lookup
          53. Madry H, Orth P, Cucchiarini M. Gene Therapy for Cartilage Repair. Cartilage 2011 Jul;2(3):201-25.
            doi: 10.1177/1947603510392914pubmed: 26069580google scholar: lookup
          54. Goodrich LR, Grieger JC, Phillips JN, Khan N, Gray SJ, McIlwraith CW, Samulski RJ. scAAVIL-1ra dosing trial in a large animal model and validation of long-term expression with repeat administration for osteoarthritis therapy. Gene Ther 2015 Jul;22(7):536-45.
            doi: 10.1038/gt.2015.21pubmed: 25902762google scholar: lookup
          55. Maninchedda U, Lepage OM, Gangl M, Hilairet S, Remandet B, Meot F, Penarier G, Segard E, Cortez P, Jorgensen C, Steinberg R. Development of an equine groove model to induce metacarpophalangeal osteoarthritis: a pilot study on 6 horses. PLoS One 2015;10(2):e0115089.
            doi: 10.1371/journal.pone.0115089pubmed: 25680102google scholar: lookup
          56. Cucchiarini M, Madry H. Use of tissue engineering strategies to repair joint tissues in osteoarthritis: viral gene transfer approaches. Curr Rheumatol Rep 2014 Oct;16(10):449.
            doi: 10.1007/s11926-014-0449-0pubmed: 25182677google scholar: lookup
          57. Hemphill DD, McIlwraith CW, Samulski RJ, Goodrich LR. Adeno-associated viral vectors show serotype specific transduction of equine joint tissue explants and cultured monolayers. Sci Rep 2014 Jul 29;4:5861.
            doi: 10.1038/srep05861pubmed: 25069854google scholar: lookup
          58. Fahy N, Farrell E, Ritter T, Ryan AE, Murphy JM. Immune modulation to improve tissue engineering outcomes for cartilage repair in the osteoarthritic joint. Tissue Eng Part B Rev 2015 Feb;21(1):55-66.
            doi: 10.1089/ten.TEB.2014.0098pubmed: 24950588google scholar: lookup
          59. Venkatesan JK, Rey-Rico A, Schmitt G, Wezel A, Madry H, Cucchiarini M. rAAV-mediated overexpression of TGF-β stably restructures human osteoarthritic articular cartilage in situ. J Transl Med 2013 Sep 13;11:211.
            doi: 10.1186/1479-5876-11-211pubmed: 24034904google scholar: lookup
          60. Baltzer AW, Ostapczuk MS, Stosch D, Seidel F, Granrath M. A new treatment for hip osteoarthritis: clinical evidence for the efficacy of autologous conditioned serum. Orthop Rev (Pavia) 2013 Jun 7;5(2):59-64.
            doi: 10.4081/or.2013.e13pubmed: 23888203google scholar: lookup
          61. Mashayekhi K, O'Brien M, Zugun-Eloae F, Labusca L. Novel approaches for treating musculoskeletal diseases: molecular orthopedics and systems medicine. Open Orthop J 2013;7:144-51.
            doi: 10.2174/1874325001307010144pubmed: 23798982google scholar: lookup
          62. McIlwraith CW, Frisbie DD, Kawcak CE. The horse as a model of naturally occurring osteoarthritis. Bone Joint Res 2012 Nov;1(11):297-309.
            doi: 10.1302/2046-3758.111.2000132pubmed: 23610661google scholar: lookup
          63. Alvarez-Camino JC, Vázquez-Delgado E, Gay-Escoda C. Use of autologous conditioned serum (Orthokine) for the treatment of the degenerative osteoarthritis of the temporomandibular joint. Review of the literature. Med Oral Patol Oral Cir Bucal 2013 May 1;18(3):e433-8.
            doi: 10.4317/medoral.18373pubmed: 23524415google scholar: lookup
          64. Lee HH, O'Malley MJ, Friel NA, Payne KA, Qiao C, Xiao X, Chu CR. Persistence, localization, and external control of transgene expression after single injection of adeno-associated virus into injured joints. Hum Gene Ther 2013 Apr;24(4):457-66.
            doi: 10.1089/hum.2012.118pubmed: 23496155google scholar: lookup
          65. Boyce MK, Trumble TN, Carlson CS, Groschen DM, Merritt KA, Brown MP. Non-terminal animal model of post-traumatic osteoarthritis induced by acute joint injury. Osteoarthritis Cartilage 2013 May;21(5):746-55.
            doi: 10.1016/j.joca.2013.02.653pubmed: 23467035google scholar: lookup
          66. Goodrich LR, Phillips JN, McIlwraith CW, Foti SB, Grieger JC, Gray SJ, Samulski RJ. Optimization of scAAVIL-1ra In Vitro and In Vivo to Deliver High Levels of Therapeutic Protein for Treatment of Osteoarthritis. Mol Ther Nucleic Acids 2013 Feb 5;2(2):e70.
            doi: 10.1038/mtna.2012.61pubmed: 23385523google scholar: lookup
          67. Haseeb A, Haqqi TM. Immunopathogenesis of osteoarthritis. Clin Immunol 2013 Mar;146(3):185-96.
            doi: 10.1016/j.clim.2012.12.011pubmed: 23360836google scholar: lookup
          68. Gregory MH, Capito N, Kuroki K, Stoker AM, Cook JL, Sherman SL. A review of translational animal models for knee osteoarthritis. Arthritis 2012;2012:764621.
            doi: 10.1155/2012/764621pubmed: 23326663google scholar: lookup
          69. Watson RS, Broome TA, Levings PP, Rice BL, Kay JD, Smith AD, Gouze E, Gouze JN, Dacanay EA, Hauswirth WW, Nickerson DM, Dark MJ, Colahan PT, Ghivizzani SC. scAAV-mediated gene transfer of interleukin-1-receptor antagonist to synovium and articular cartilage in large mammalian joints. Gene Ther 2013 Jun;20(6):670-7.
            doi: 10.1038/gt.2012.81pubmed: 23151520google scholar: lookup
          70. Whitmire RE, Wilson DS, Singh A, Levenston ME, Murthy N, García AJ. Self-assembling nanoparticles for intra-articular delivery of anti-inflammatory proteins. Biomaterials 2012 Oct;33(30):7665-75.
            doi: 10.1016/j.biomaterials.2012.06.101pubmed: 22818981google scholar: lookup
          71. Jotanovic Z, Mihelic R, Sestan B, Dembic Z. Role of interleukin-1 inhibitors in osteoarthritis: an evidence-based review. Drugs Aging 2012 May 1;29(5):343-58.
            doi: 10.2165/11599350-000000000-00000pubmed: 22550965google scholar: lookup
          72. Longo UG, Petrillo S, Franceschetti E, Berton A, Maffulli N, Denaro V. Stem cells and gene therapy for cartilage repair. Stem Cells Int 2012;2012:168385.
            doi: 10.1155/2012/168385pubmed: 22481959google scholar: lookup
          73. Weimer A, Madry H, Venkatesan JK, Schmitt G, Frisch J, Wezel A, Jung J, Kohn D, Terwilliger EF, Trippel SB, Cucchiarini M. Benefits of recombinant adeno-associated virus (rAAV)-mediated insulinlike growth factor I (IGF-I) overexpression for the long-term reconstruction of human osteoarthritic cartilage by modulation of the IGF-I axis. Mol Med 2012 May 9;18(1):346-58.
            doi: 10.2119/molmed.2011.00371pubmed: 22160392google scholar: lookup
          74. Cohen SB, Proudman S, Kivitz AJ, Burch FX, Donohue JP, Burstein D, Sun YN, Banfield C, Vincent MS, Ni L, Zack DJ. A randomized, double-blind study of AMG 108 (a fully human monoclonal antibody to IL-1R1) in patients with osteoarthritis of the knee. Arthritis Res Ther 2011 Jul 29;13(4):R125.
            doi: 10.1186/ar3430pubmed: 21801403google scholar: lookup
          75. Santangelo KS, Pieczarka EM, Nuovo GJ, Weisbrode SE, Bertone AL. Temporal expression and tissue distribution of interleukin-1β in two strains of guinea pigs with varying propensity for spontaneous knee osteoarthritis. Osteoarthritis Cartilage 2011 Apr;19(4):439-48.
            doi: 10.1016/j.joca.2011.01.004pubmed: 21251992google scholar: lookup
          76. Evans CH, Ghivizzani SC, Robbins PD. Getting arthritis gene therapy into the clinic. Nat Rev Rheumatol 2011 Apr;7(4):244-9.
            doi: 10.1038/nrrheum.2010.193pubmed: 21135882google scholar: lookup
          77. Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol 2011 Jan;7(1):33-42.
            doi: 10.1038/nrrheum.2010.196pubmed: 21119608google scholar: lookup
          78. Miller RE, Grodzinsky AJ, Vanderploeg EJ, Lee C, Ferris DJ, Barrett MF, Kisiday JD, Frisbie DD. Effect of self-assembling peptide, chondrogenic factors, and bone marrow-derived stromal cells on osteochondral repair. Osteoarthritis Cartilage 2010 Dec;18(12):1608-19.
            doi: 10.1016/j.joca.2010.09.004pubmed: 20851201google scholar: lookup
          79. Umlauf D, Frank S, Pap T, Bertrand J. Cartilage biology, pathology, and repair. Cell Mol Life Sci 2010 Dec;67(24):4197-211.
            doi: 10.1007/s00018-010-0498-0pubmed: 20734104google scholar: lookup
          80. Chen B, Qin J, Wang H, Magdalou J, Chen L. Effects of adenovirus-mediated bFGF, IL-1Ra and IGF-1 gene transfer on human osteoarthritic chondrocytes and osteoarthritis in rabbits. Exp Mol Med 2010 Oct 31;42(10):684-95.
            doi: 10.3858/emm.2010.42.10.067pubmed: 20733349google scholar: lookup
          81. Kötter I, Horneff G. [IL-1 antagonists]. Z Rheumatol 2010 Sep;69(7):581-93.
            doi: 10.1007/s00393-009-0530-7pubmed: 20703489google scholar: lookup
          82. Rutgers M, Saris DB, Dhert WJ, Creemers LB. Cytokine profile of autologous conditioned serum for treatment of osteoarthritis, in vitro effects on cartilage metabolism and intra-articular levels after injection. Arthritis Res Ther 2010;12(3):R114.
            doi: 10.1186/ar3050pubmed: 20537160google scholar: lookup
          83. Calich AL, Domiciano DS, Fuller R. Osteoarthritis: can anti-cytokine therapy play a role in treatment?. Clin Rheumatol 2010 May;29(5):451-5.
            doi: 10.1007/s10067-009-1352-3pubmed: 20108016google scholar: lookup
          84. Villasante A, Araneda OF, Behn C, Galleguillos M, Adarmes H. Antioxidant capacity and oxidative damage determination in synovial fluid of chronically damaged equine metacarpophalangeal joint. Vet Res Commun 2010 Feb;34(2):133-41.
            doi: 10.1007/s11259-009-9338-9pubmed: 20012721google scholar: lookup
          85. Cucchiarini M, Heiligenstein S, Kohn D, Madry H. [Molecular tools to remodel osteoarthritic articular cartilage : growth, transcription, and signaling factors]. Orthopade 2009 Nov;38(11):1063-70.
            doi: 10.1007/s00132-009-1495-6pubmed: 19876615google scholar: lookup
          86. Koch TG, Berg LC, Betts DH. Current and future regenerative medicine - principles, concepts, and therapeutic use of stem cell therapy and tissue engineering in equine medicine. Can Vet J 2009 Feb;50(2):155-65.
            pubmed: 19412395
          87. de Grauw JC, van de Lest CH, van Weeren PR. Inflammatory mediators and cartilage biomarkers in synovial fluid after a single inflammatory insult: a longitudinal experimental study. Arthritis Res Ther 2009;11(2):R35.
            doi: 10.1186/ar2640pubmed: 19272138google scholar: lookup
          88. Kisiday JD, Frisbie DD, McIlwraith CW, Grodzinsky AJ. Dynamic compression stimulates proteoglycan synthesis by mesenchymal stem cells in the absence of chondrogenic cytokines. Tissue Eng Part A 2009 Oct;15(10):2817-24.
            doi: 10.1089/ten.TEA.2008.0357pubmed: 19243241google scholar: lookup
          89. Evans CH, Ghivizzani SC, Robbins PD. Gene therapy of the rheumatic diseases: 1998 to 2008. Arthritis Res Ther 2009;11(1):209.
            doi: 10.1186/ar2563pubmed: 19232068google scholar: lookup
          90. Evans CH, Ghivizzani SC, Robbins PD. Orthopedic gene therapy in 2008. Mol Ther 2009 Feb;17(2):231-44.
            doi: 10.1038/mt.2008.265pubmed: 19066598google scholar: lookup
          91. Wehling P, Reinecke J, Baltzer AW, Granrath M, Schulitz KP, Schultz C, Krauspe R, Whiteside TW, Elder E, Ghivizzani SC, Robbins PD, Evans CH. Clinical responses to gene therapy in joints of two subjects with rheumatoid arthritis. Hum Gene Ther 2009 Feb;20(2):97-101.
            doi: 10.1089/hum.2008.075pubmed: 18986219google scholar: lookup
          92. Blagbrough IS, Zara C. Animal models for target diseases in gene therapy--using DNA and siRNA delivery strategies. Pharm Res 2009 Jan;26(1):1-18.
            doi: 10.1007/s11095-008-9646-8pubmed: 18841450google scholar: lookup
          93. Cucchiarini M, Terwilliger EF, Kohn D, Madry H. Remodelling of human osteoarthritic cartilage by FGF-2, alone or combined with Sox9 via rAAV gene transfer. J Cell Mol Med 2009 Aug;13(8B):2476-2488.
            doi: 10.1111/j.1582-4934.2008.00474.xpubmed: 18705695google scholar: lookup
          94. Ghivizzani SC, Gouze E, Gouze JN, Kay JD, Bush ML, Watson RS, Levings PP, Nickerson DM, Colahan PT, Robbins PD, Evans CH. Perspectives on the use of gene therapy for chronic joint diseases. Curr Gene Ther 2008 Aug;8(4):273-86.
            doi: 10.2174/156652308785160638pubmed: 18691023google scholar: lookup
          95. Steinert AF, Nöth U, Tuan RS. Concepts in gene therapy for cartilage repair. Injury 2008 Apr;39 Suppl 1(Suppl 1):S97-113.
            doi: 10.1016/j.injury.2008.01.034pubmed: 18313477google scholar: lookup
          96. Lejeune JP, Franck T, Gangl M, Schneider N, Michaux C, Deby-Dupont G, Serteyn D. Plasma concentration of insulin-like growth factor I (IGF-I) in growing Ardenner horses suffering from juvenile digital degenerative osteoarthropathy. Vet Res Commun 2007 Feb;31(2):185-95.
            doi: 10.1007/s11259-006-3385-2pubmed: 17216321google scholar: lookup
          97. Evans CH. Gene therapies for osteoarthritis. Curr Rheumatol Rep 2004 Feb;6(1):31-40.
            doi: 10.1007/s11926-004-0081-5pubmed: 14713400google scholar: lookup
          98. Gouze JN, Gouze E, Palmer GD, Liew VS, Pascher A, Betz OB, Thornhill TS, Evans CH, Grodzinsky AJ, Ghivizzani SC. A comparative study of the inhibitory effects of interleukin-1 receptor antagonist following administration as a recombinant protein or by gene transfer. Arthritis Res Ther 2003;5(5):R301-9.
            doi: 10.1186/ar795pubmed: 12932294google scholar: lookup
          99. Zhang Y, Han Y, Sun Y, Hao L, Gao Y, Ye J, Wang H, Zhang T, Liu Y, Yang Y. Osteoarthritis: molecular pathogenesis and potential therapeutic options. Signal Transduct Target Ther 2026 Mar 4;11(1).
            doi: 10.1038/s41392-025-02556-6pubmed: 41781374google scholar: lookup
          100. Pasternak M, Chęciński M, Chęcińska K, Turosz N, Chyży I, Kosiński B, Kwiatkowska K, Romańczyk K, Hoppe A, Sikora M. Preliminary Evidence on Intra-Articular Autologous Conditioned Serum (ACS) in Temporomandibular Joint Disorders (TMDs): A Systematic Review with a Focus on Mechanisms and Potential Application in Clinical Practice. Int J Mol Sci 2025 Sep 10;26(18).
            doi: 10.3390/ijms26188798pubmed: 41009367google scholar: lookup
          101. Reihs E, Fischer A, Gerner I, Windhager R, Toegel S, Zaucke F, Rothbauer M, Jenner F. Beyond symptomatic alignment: evaluating the integration of causal mechanisms in matching animal models with human pathotypes in osteoarthritis research. Arthritis Res Ther 2025 May 17;27(1):109.
            doi: 10.1186/s13075-025-03561-4pubmed: 40382623google scholar: lookup
          102. Luedke LK, Seabaugh KA, Cooper BG, Snyder BD, Wimmer MA, McIlwraith CW, Barrett MF, Kawcak CE, Grinstaff MW, Goodrich LR. A Safety and Efficacy Study of a Synthetic Biolubricant in an Equine Model of Post-Traumatic Osteoarthritis. Animals (Basel) 2025 Feb 1;15(3).
            doi: 10.3390/ani15030404pubmed: 39943174google scholar: lookup
          103. Ubhe A. IL-1 receptor antagonist: etiological and drug delivery systems overview. Inflamm Res 2024 Dec;73(12):2231-2247.
            doi: 10.1007/s00011-024-01960-ypubmed: 39455436google scholar: lookup
          104. Pfeifer JPH, Stievani FC, Fernandes CJDC, Rosa GDS, Apolonio EVP, Rossi MC, Zambuzzi WF, Alves ALG. Influence of inflammation on the expression of microRNA-140 in extracellular vesicles from 2D and 3D culture models of synovial-membrane-derived stem cells. Front Bioeng Biotechnol 2024;12:1416694.
            doi: 10.3389/fbioe.2024.1416694pubmed: 39170063google scholar: lookup
          105. Panizzi L, Vignes M, Dittmer KE, Waterland MR, Rogers CW, Sano H, McIlwraith CW, Riley CB. Infrared Spectroscopy of Synovial Fluid Shows Accuracy as an Early Biomarker in an Equine Model of Traumatic Osteoarthritis. Animals (Basel) 2024 Mar 22;14(7).
            doi: 10.3390/ani14070986pubmed: 38612225google scholar: lookup
          106. Andersen C, Walters M, Bundgaard L, Berg LC, Vonk LA, Lundgren-Åkerlund E, Henriksen BL, Lindegaard C, Skovgaard K, Jacobsen S. Intraarticular treatment with integrin α10β1-selected mesenchymal stem cells affects microRNA expression in experimental post-traumatic osteoarthritis in horses. Front Vet Sci 2024;11:1374681.
            doi: 10.3389/fvets.2024.1374681pubmed: 38596460google scholar: lookup
          107. Connard SS, Gaesser AM, Clarke EJ, Linardi RL, Even KM, Engiles JB, Koch DW, Peffers MJ, Ortved KF. Plasma and synovial fluid extracellular vesicles display altered microRNA profiles in horses with naturally occurring post-traumatic osteoarthritis: an exploratory study. J Am Vet Med Assoc 2024 Jun 1;262(S1):S83-S96.
            doi: 10.2460/javma.24.02.0102pubmed: 38593834google scholar: lookup
          108. Stewart HL, Gilbert D, Stefanovski D, Garman Z, Albro MB, Bais M, Grinstaff MW, Snyder BD, Schaer TP. A missed opportunity: A scoping review of the effect of sex and age on osteoarthritis using large animal models. Osteoarthritis Cartilage 2024 May;32(5):501-513.
            doi: 10.1016/j.joca.2024.02.009pubmed: 38408635google scholar: lookup
          109. Wettengel JM, Naka H, Dissen GA, Torgerson J, Pounder M, Mueller SF, Mueller E, Hagen P, Brandt M, Protzer U, Burwitz BJ. High-Throughput Screening for the Prevalence of Neutralizing Antibodies against Human Adenovirus Serotype 5. Vaccines (Basel) 2024 Feb 1;12(2).
            doi: 10.3390/vaccines12020155pubmed: 38400138google scholar: lookup
          110. DeJulius CR, Walton BL, Colazo JM, d'Arcy R, Francini N, Brunger JM, Duvall CL. Engineering approaches for RNA-based and cell-based osteoarthritis therapies. Nat Rev Rheumatol 2024 Feb;20(2):81-100.
            doi: 10.1038/s41584-023-01067-4pubmed: 38253889google scholar: lookup
          111. Della Tommasa S, Brehm W, Farì G, Bernetti A, Imperante A. Use of Autologous Conditioned Serum (ACS) for Osteoarthritis Treatment in Horses: A Systematic Review of Clinical Data. Vet Sci 2023 Dec 18;10(12).
            doi: 10.3390/vetsci10120707pubmed: 38133258google scholar: lookup
          112. Andersen C, Jacobsen S, Uvebrant K, Griffin JF 4th, Vonk LA, Walters M, Berg LC, Lundgren-Åkerlund E, Lindegaard C. Integrin α10β1-Selected Mesenchymal Stem Cells Reduce Pain and Cartilage Degradation and Increase Immunomodulation in an Equine Osteoarthritis Model. Cartilage 2025 Jun;16(2):250-264.
            doi: 10.1177/19476035231209402pubmed: 37990503google scholar: lookup
          113. Kearney CM, Korthagen NM, Plomp SGM, Labberté MC, de Grauw JC, van Weeren PR, Brama PAJ. A Translational Model for Repeated Episodes of Joint Inflammation: Welfare, Clinical and Synovial Fluid Biomarker Assessment. Animals (Basel) 2023 Oct 12;13(20).
            doi: 10.3390/ani13203190pubmed: 37893914google scholar: lookup
          114. O'Brien TJ, Hollinshead F, Goodrich LR. Extracellular vesicles in the treatment and prevention of osteoarthritis: can horses help us translate this therapy to humans?. Extracell Vesicles Circ Nucl Acids 2023 Jun;4(2):151-169.
            doi: 10.20517/evcna.2023.11pubmed: 37829144google scholar: lookup
          115. Bonato A, Fisch P, Ponta S, Fercher D, Manninen M, Weber D, Eklund KK, Barreto G, Zenobi-Wong M. Engineering Inflammation-Resistant Cartilage: Bridging Gene Therapy and Tissue Engineering. Adv Healthc Mater 2023 Jul;12(17):e2202271.
            doi: 10.1002/adhm.202202271pubmed: 36841937google scholar: lookup
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