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Clinical orthopaedics and related research2007; 462; 221-228; doi: 10.1097/BLO.0b013e3180dca05f

IL-1ra/IGF-1 gene therapy modulates repair of microfractured chondral defects.

Abstract: Repair of cartilage defects involves sequential participation of specific hormones and growth factors with potential impairment by inflammatory cytokines. We explored an in vivo gene therapy treatment to supply adenoviral vectors carrying the genes of interleukin-1 receptor antagonist protein (IL-1ra) and insulinlike growth factor-1 (IGF-1), hoping to enhance repair of full-thickness equine chondral defects treated with microfracture. We asked whether our treatment could (1) increase proteoglycan and Type II collagen content in the repair tissue, (2) improve the macroscopic and histomorphometric aspect of the repair tissue, and (3) induce prolonged and increased IL-1ra and IGF-1 production in treated joints. Twelve horses had full-thickness chondral defects created in their carpus and stifle followed by microfracture. Joints were injected with either equine IL-1ra/IGF-1 adenoviral preparation or Gey's balanced salt solution. Sixteen weeks later, defect healing was evaluated macroscopically, histologically, histochemically, and biochemically. Production of IL-1ra and IGF-1 was measured by enzyme-linked immunosorbent assay and radioimmunoassay. We found increased proteoglycan content in treated defects along with augmented Type II collagen associated with substantial transgene expression of IL-1ra during the first 3 weeks. These data suggest in vivo gene therapy can improve biologic processes associated with chondral defect repair.
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Publication Date: 2007-05-31 PubMed ID: 17534189DOI: 10.1097/BLO.0b013e3180dca05fGoogle 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.

This research paper investigates gene therapy as a method for improving the repair process of cartilage defects in horses. The researchers specifically tested the use of two genes, interleukin-1 receptor antagonist protein (IL-1ra) and insulinlike growth factor-1 (IGF-1), to foster better repair and recovery.

Research Background

  • The study aims to advance the understanding of cartilage defects repair which involves hormones, growth factors, and potentially harmful inflammatory cytokines.
  • The scientists tested in vivo gene therapy to supply adenoviral vectors or gene carriers, which contain genes for IL-1ra and IGF-1.
  • These genes were selected because potential benefits include increased proteoglycan and Type II collagen content in the repair tissue; improved macroscopic and histomorphometric properties; prolonged activated IL-1ra and IGF-1 production in treated joints.

Research Methodology

  • Full-thickness chondral defects were created in the joins of twelve horses, and microfracture was applied as a treatment model.
  • The joints were injected with either the adenoviral preparation delivering equine IL-1ra/IGF-1 gene therapy, or Gey’s balanced salt solution as a control.
  • After 16 weeks, healing was evaluated macroscopically (visible changes), histologically (tissue structure), histochemically (chemical changes in tissue), and biochemically (molecular composition).
  • Production of IL-1ra and IGF-1 was detected and measured through enzyme-linked immunosorbent assay and radioimmunoassay.

Results and Conclusions

  • The findings reveal increased proteoglycan content in the defects treated with gene therapy. Proteoglycans are vital for the structure and function of cartilage, indicating positive repair progression.
  • The therapy also led to an increase in Type II collagen, which is crucial for cartilage strength and resistance.
  • A notable increase in the expression of IL-1ra was observed during the first 3 weeks following therapy. However, the study does not provide data on IGF-1 expression.
  • The results imply that in vivo gene therapy, delivering IL-1ra and potentially IGF-1, can enhance the biologic processes associated with cartilage defect repair.

Cite This Article

APA
Morisset S, Frisbie DD, Robbins PD, Nixon AJ, McIlwraith CW. (2007). IL-1ra/IGF-1 gene therapy modulates repair of microfractured chondral defects. Clin Orthop Relat Res, 462, 221-228. https://doi.org/10.1097/BLO.0b013e3180dca05f

Publication

Clinical orthopaedics and related research
ISSN: 0009-921X
NlmUniqueID: 0075674
Country: United States
Language: English
Volume: 462
Pages: 221-228

Researcher Affiliations

Morisset, Sophie
  • Orthopaedic Research Center, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80524, USA.
Frisbie, David D
    Robbins, Paul D
      Nixon, Alan J
        McIlwraith, C Wayne

          MeSH Terms

          • Animals
          • Carpus, Animal / injuries
          • Carpus, Animal / pathology
          • Carpus, Animal / surgery
          • Cartilage, Articular / injuries
          • Cartilage, Articular / metabolism
          • Cartilage, Articular / pathology
          • Chondrocytes / metabolism
          • Chondrocytes / pathology
          • Chondrogenesis / genetics
          • Collagen Type II / metabolism
          • Disease Models, Animal
          • Enzyme-Linked Immunosorbent Assay
          • Femoral Fractures / pathology
          • Femoral Fractures / physiopathology
          • Femoral Fractures / surgery
          • Gene Expression
          • Genetic Therapy / methods
          • Genetic Vectors
          • Hindlimb
          • Horses
          • Insulin-Like Growth Factor I / genetics
          • Interleukin 1 Receptor Antagonist Protein / genetics
          • Proteoglycans / metabolism
          • Stifle / injuries
          • Stifle / pathology
          • Stifle / surgery
          • Up-Regulation
          • Wound Healing

          Citations

          This article has been cited 40 times.
          1. Hosseinkhani H, Domb AJ, Sharifzadeh G, Nahum V. Gene Therapy for Regenerative Medicine. Pharmaceutics 2023 Mar 6;15(3).
            doi: 10.3390/pharmaceutics15030856pubmed: 36986717google scholar: lookup
          2. Sun K, Wang C, Xiao J, Brodt MD, Yuan L, Yang T, Alippe Y, Hu H, Hao D, Abu-Amer Y, Silva MJ, Shen J, Mbalaviele G. Fracture healing is delayed in the absence of gasdermin-interleukin-1 signaling. Elife 2022 Mar 4;11.
            doi: 10.7554/eLife.75753pubmed: 35244027google scholar: lookup
          3. Liu S, Deng Z, Chen K, Jian S, Zhou F, Yang Y, Fu Z, Xie H, Xiong J, Zhu W. Cartilage tissue engineering: From proinflammatory and anti‑inflammatory cytokines to osteoarthritis treatments (Review). Mol Med Rep 2022 Mar;25(3).
            doi: 10.3892/mmr.2022.12615pubmed: 35088882google scholar: lookup
          4. 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
          5. Chen T, Weng W, Liu Y, Aspera-Werz RH, Nüssler AK, Xu J. Update on Novel Non-Operative Treatment for Osteoarthritis: Current Status and Future Trends. Front Pharmacol 2021;12:755230.
            doi: 10.3389/fphar.2021.755230pubmed: 34603064google scholar: lookup
          6. Zlotnick HM, Locke RC, Stoeckl BD, Patel JM, Gupta S, Browne KD, Koh J, Carey JL, Mauck RL. Marked differences in local bone remodelling in response to different marrow stimulation techniques in a large animal. Eur Cell Mater 2021 May 19;41:546-557.
            doi: 10.22203/eCM.v041a35pubmed: 34008855google scholar: lookup
          7. Szwedowski D, Szczepanek J, Paczesny Ł, Pękała P, Zabrzyński J, Kruczyński J. Genetics in Cartilage Lesions: Basic Science and Therapy Approaches. Int J Mol Sci 2020 Jul 30;21(15).
            doi: 10.3390/ijms21155430pubmed: 32751537google scholar: lookup
          8. Shah SS, Mithoefer K. Current Applications of Growth Factors for Knee Cartilage Repair and Osteoarthritis Treatment. Curr Rev Musculoskelet Med 2020 Dec;13(6):641-650.
            doi: 10.1007/s12178-020-09664-6pubmed: 32710292google scholar: lookup
          9. 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
          10. Boffa A, Previtali D, Altamura SA, Zaffagnini S, Candrian C, Filardo G. Platelet-Rich Plasma Augmentation to Microfracture Provides a Limited Benefit for the Treatment of Cartilage Lesions: A Meta-analysis. Orthop J Sports Med 2020 Apr;8(4):2325967120910504.
            doi: 10.1177/2325967120910504pubmed: 32341925google scholar: lookup
          11. Shortt C, Luyt LG, Turley EA, Cowman MK, Kirsch T. A Hyaluronan-binding Peptide (P15-1) Reduces Inflammatory and Catabolic Events in IL-1β-treated Human Articular Chondrocytes. Sci Rep 2020 Jan 29;10(1):1441.
            doi: 10.1038/s41598-020-57586-7pubmed: 31996703google scholar: lookup
          12. Venkatesan JK, Rey-Rico A, Cucchiarini M. Current Trends in Viral Gene Therapy for Human Orthopaedic Regenerative Medicine. Tissue Eng Regen Med 2019 Aug;16(4):345-355.
            doi: 10.1007/s13770-019-00179-xpubmed: 31413939google scholar: lookup
          13. Cucchiarini M, Madry H. Biomaterial-guided delivery of gene vectors for targeted articular cartilage repair. Nat Rev Rheumatol 2019 Jan;15(1):18-29.
            doi: 10.1038/s41584-018-0125-2pubmed: 30514957google scholar: lookup
          14. Bellavia D, Veronesi F, Carina V, Costa V, Raimondi L, De Luca A, Alessandro R, Fini M, Giavaresi G. Gene therapy for chondral and osteochondral regeneration: is the future now?. Cell Mol Life Sci 2018 Feb;75(4):649-667.
            doi: 10.1007/s00018-017-2637-3pubmed: 28864934google scholar: lookup
          15. Cruz IB, Severo AL, Azzolin VF, Garcia LF, Kuhn A, Lech O. Regenerative potential of the cartilaginous tissue in mesenchymal stem cells: update, limitations, and challenges. Rev Bras Ortop 2017 Jan-Feb;52(1):2-10.
            doi: 10.1016/j.rboe.2016.11.005pubmed: 28194374google scholar: lookup
          16. Roach BL, Kelmendi-Doko A, Balutis EC, Marra KG, Ateshian GA, Hung CT. Dexamethasone Release from Within Engineered Cartilage as a Chondroprotective Strategy Against Interleukin-1α. Tissue Eng Part A 2016 Apr;22(7-8):621-32.
            doi: 10.1089/ten.TEA.2016.0018pubmed: 26956216google scholar: lookup
          17. Clark A, Hilt JZ, Milbrandt TA, Puleo DA. Treating Proximal Tibial Growth Plate Injuries Using Poly(Lactic-co-Glycolic Acid) Scaffolds. Biores Open Access 2015;4(1):65-74.
            doi: 10.1089/biores.2014.0034pubmed: 26309783google scholar: lookup
          18. Grande DA, Schwartz JA, Brandel E, Chahine NO, Sgaglione N. Articular Cartilage Repair: Where We Have Been, Where We Are Now, and Where We Are Headed. Cartilage 2013 Oct;4(4):281-5.
            doi: 10.1177/1947603513494402pubmed: 26069673google scholar: lookup
          19. 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
          20. Zaslav K, McAdams T, Scopp J, Theosadakis J, Mahajan V, Gobbi A. New Frontiers for Cartilage Repair and Protection. Cartilage 2012 Jan;3(1 Suppl):77S-86S.
            doi: 10.1177/1947603511411050pubmed: 26069613google scholar: lookup
          21. McIlwraith CW, Fortier LA, Frisbie DD, Nixon AJ. Equine Models of Articular Cartilage Repair. Cartilage 2011 Oct;2(4):317-26.
            doi: 10.1177/1947603511406531pubmed: 26069590google scholar: lookup
          22. 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
          23. Strauss EJ, Barker JU, Kercher JS, Cole BJ, Mithoefer K. Augmentation Strategies following the Microfracture Technique for Repair of Focal Chondral Defects. Cartilage 2010 Apr;1(2):145-52.
            doi: 10.1177/1947603510366718pubmed: 26069546google scholar: lookup
          24. McIlwraith CW, Frisbie DD. Microfracture: Basic Science Studies in the Horse. Cartilage 2010 Apr;1(2):87-95.
            doi: 10.1177/1947603510367427pubmed: 26069539google scholar: lookup
          25. 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
          26. Mithoefer K, Peterson L, Zenobi-Wong M, Mandelbaum BR. Cartilage issues in football-today's problems and tomorrow's solutions. Br J Sports Med 2015 May;49(9):590-6.
            doi: 10.1136/bjsports-2015-094772pubmed: 25878075google scholar: lookup
          27. Hoffman JK, Geraghty S, Protzman NM. Articular cartilage repair using marrow stimulation augmented with a viable chondral allograft: 9-month postoperative histological evaluation. Case Rep Orthop 2015;2015:617365.
            doi: 10.1155/2015/617365pubmed: 25628907google scholar: lookup
          28. Kondo M, Yamaoka K, Tanaka Y. Acquiring chondrocyte phenotype from human mesenchymal stem cells under inflammatory conditions. Int J Mol Sci 2014 Nov 17;15(11):21270-85.
            doi: 10.3390/ijms151121270pubmed: 25407530google scholar: lookup
          29. 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
          30. Clark A, Milbrandt TA, Hilt JZ, Puleo DA. Retention of insulin-like growth factor I bioactivity during the fabrication of sintered polymeric scaffolds. Biomed Mater 2014 Apr;9(2):025015.
            doi: 10.1088/1748-6041/9/2/025015pubmed: 24565886google scholar: lookup
          31. 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
          32. 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
          33. Cucchiarini M, Orth P, Madry H. Direct rAAV SOX9 administration for durable articular cartilage repair with delayed terminal differentiation and hypertrophy in vivo. J Mol Med (Berl) 2013 May;91(5):625-36.
            doi: 10.1007/s00109-012-0978-9pubmed: 23149825google scholar: lookup
          34. van Eekeren IC, Reilingh ML, van Dijk CN. Rehabilitation and return-to-sports activity after debridement and bone marrow stimulation of osteochondral talar defects. Sports Med 2012 Oct 1;42(10):857-70.
            doi: 10.1007/BF03262299pubmed: 22963224google scholar: lookup
          35. Venkatesan JK, Ekici M, Madry H, Schmitt G, Kohn D, Cucchiarini M. SOX9 gene transfer via safe, stable, replication-defective recombinant adeno-associated virus vectors as a novel, powerful tool to enhance the chondrogenic potential of human mesenchymal stem cells. Stem Cell Res Ther 2012;3(3):22.
            doi: 10.1186/scrt113pubmed: 22742415google scholar: lookup
          36. Allon AA, Ng KW, Hammoud S, Russell BH, Jones CM, Rivera JJ, Schwartz J, Hook M, Maher SA. Augmenting the articular cartilage-implant interface: Functionalizing with a collagen adhesion protein. J Biomed Mater Res A 2012 Aug;100(8):2168-75.
            doi: 10.1002/jbm.a.34144pubmed: 22615182google scholar: lookup
          37. 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
          38. Verwilghen DR, Vanderheyden L, Franck T, Busoni V, Enzerink E, Gangl M, Lejeune JP, van Galen G, Grulke S, Serteyn D. Variations of plasmatic concentrations of Insulin-like Growth Factor-I in post-pubescent horses affected with developmental osteochondral lesions. Vet Res Commun 2009 Oct;33(7):701-9.
            doi: 10.1007/s11259-009-9219-2pubmed: 19319655google scholar: lookup
          39. 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
          40. Primorac D, Molnar V, Tsoukas D, Uzieliene I, Tremolada C, Brlek P, Klarić E, Vidović D, Zekušić M, Pachaleva J, Bernotiene E, Wilson A, Mobasheri A. Tissue engineering and future directions in regenerative medicine for knee cartilage repair: a comprehensive review. Croat Med J 2024 Jun 13;65(3):268-287.
            doi: 10.3325/cmj.2024.65.268pubmed: 38868973google scholar: lookup
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