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Journal of orthopaedic research : official publication of the Orthopaedic Research Society2004; 23(1); 118-126; doi: 10.1016/j.orthres.2004.06.020

Dual transduction of insulin-like growth factor-I and interleukin-1 receptor antagonist protein controls cartilage degradation in an osteoarthritic culture model.

Abstract: This study evaluated the potential of gene induced synoviocyte expression of a combination of insulin-like growth factor-I (AdIGF-I) and interleukin-1 receptor antagonist protein (AdIL-1Ra) to control articular cartilage degradation in vitro. Cartilage explants and synovial membrane were harvested from young mature horses. Synovial monolayers were established and either (1) maintained as untransduced controls; (2) transduced with AdIGF-I at 200 MOI in 500 microl serum-free medium; (3) transduced with AdIL-1Ra at 100 MOI; or (4) transduced with a combination of AdIGF-I (200 MOI) and AdIL-1Ra (100 MOI). Following transduction, cartilage explants were exposed to the synovial monolayer medium using co-culture inserts. Cultures were maintained for 6 days in either serum-free medium or medium containing 10 ng/ml recombinant human interleukin-1beta. At termination, synovial cell RNA was isolated for real-time PCR analysis, and cartilage explants were collected for H&E and toluidine blue staining, immunohistochemistry for type II collagen and IGF-I, in situ localization of IGF-I and type II collagen gene expression, and biochemical assays. Synovial monolayers were readily transduced with both AdIGF-I and AdIL-1Ra. IGF-I and IL-1Ra protein were secreted at beneficial levels throughout the experiment, having peak concentrations of 94.6 ng/ml and 33.0 ng/ml, respectively. Transduction with IGF-I promoted cartilage production of proteoglycan and type II collagen, suggesting a beneficial role for healing injured cartilage. Transduction with IL-1Ra decreased the synovial expression of IL-1alpha and IL-1beta and matrix metalloproteinases, indicating a mechanism for prevention of matrix degradation. The beneficial effects of the combination of anabolic growth factors and catabolic blockers were evident in improved preservation of proteoglycan content of cartilage explants exposed to the depleting effects of IL-1. These results show that gene therapy combining anabolic growth factors to stimulate matrix synthesis and catabolic blockers to prevent matrix degradation by IL-1, protects and causes partial restoration of cartilage matrix, and suggest a potential benefit of combination gene therapy for cartilage healing.
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Publication Date: 2004-12-21 PubMed ID: 15607883DOI: 10.1016/j.orthres.2004.06.020Google 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 research examines the impact of introducing insulin-like growth factor-I and interleukin-1 receptor antagonist protein on controlling cartilage degradation using a laboratory model that replicates the conditions of osteoarthritis.

Research Methodology

  • The researchers harvested cartilage explants and synovial membrane from young mature horses.
  • There were four groups of synovial monolayers: untransduced controls, those introduced with AdIGF-I, those with AdIL-1Ra, and a combination of AdIGF-I and AdIL-1Ra.
  • Post-transduction, the cartilage explants were exposed to a synovial monolayer medium via co-culture inserts.
  • The cultures were maintained for six days, and some were exposed to a medium featuring recombinant human interleukin-1beta.
  • Upon termination, synovial cell RNA was taken for real-time PCR analysis, and the cartilage explants underwent multiple tests and stains.

Findings

  • The synovial monolayers successfully took in both AdIGF-I and AdIL-1Ra.
  • IGF-I and IL-1Ra protein were observed in beneficial levels throughout the experiment, peaking at 94.6 ng/ml and 33.0 ng/ml, respectively.
  • Transduction with IGF-I appeared to promote proteoglycan and type II collagen production in the cartilage, suggesting it supports cartilage healing.
  • Transduction with IL-1Ra saw a decrease in the synovial expression of IL-1alpha, IL-1beta, and matrix metalloproteases, indicating that it can help prevent matrix degradation.

Conclusion

  • The positive effects of combining anabolic growth factors and catabolic blockers were observed in the improved preservation of proteoglycan content in cartilage explants that were exposed to IL-1.
  • The results demonstrate that gene therapy using both anabolic growth factors (to promote matrix synthesis) and catabolic blockers (to prevent matrix degradation by IL-1) can protect and partially restore the cartilage matrix. Therefore, these findings suggest that this combined gene therapy may be beneficial for cartilage healing.

Cite This Article

APA
Haupt JL, Frisbie DD, McIlwraith CW, Robbins PD, Ghivizzani S, Evans CH, Nixon AJ. (2004). Dual transduction of insulin-like growth factor-I and interleukin-1 receptor antagonist protein controls cartilage degradation in an osteoarthritic culture model. J Orthop Res, 23(1), 118-126. https://doi.org/10.1016/j.orthres.2004.06.020

Publication

Journal of orthopaedic research : official publication of the Orthopaedic Research Society
ISSN: 0736-0266
NlmUniqueID: 8404726
Country: United States
Language: English
Volume: 23
Issue: 1
Pages: 118-126

Researcher Affiliations

Haupt, Jennifer L
  • Comparative Orthopaedics Laboratory, College of Veterinary Medicine, Cornell University, C3-176 Veterinary Medical Center, Ithaca, NY 14853, USA.
Frisbie, David D
    McIlwraith, C Wayne
      Robbins, Paul D
        Ghivizzani, Steve
          Evans, Chris H
            Nixon, Alan J

              MeSH Terms

              • Animals
              • Cartilage / metabolism
              • Cartilage / pathology
              • DNA / analysis
              • Genetic Therapy
              • Horses
              • Insulin-Like Growth Factor I / genetics
              • Interleukin 1 Receptor Antagonist Protein
              • Osteoarthritis / therapy
              • Proteoglycans / analysis
              • RNA, Messenger / analysis
              • Sialoglycoproteins / genetics
              • Tissue Culture Techniques

              Citations

              This article has been cited 37 times.
              1. 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
              2. Xiong Y, Mi BB, Lin Z, Hu YQ, Yu L, Zha KK, Panayi AC, Yu T, Chen L, Liu ZP, Patel A, Feng Q, Zhou SH, Liu GH. The role of the immune microenvironment in bone, cartilage, and soft tissue regeneration: from mechanism to therapeutic opportunity. Mil Med Res 2022 Nov 19;9(1):65.
                doi: 10.1186/s40779-022-00426-8pubmed: 36401295google scholar: lookup
              3. Evans CH, Ghivizzani SC, Robbins PD. Orthopaedic Gene Therapy: Twenty-Five Years On. JBJS Rev 2021 Aug 26;9(8).
                doi: 10.2106/JBJS.RVW.20.00220pubmed: 34437305google scholar: lookup
              4. Wang Q, Xu B, Fan K, Wu J, Wang T. CypB-CD147 Signaling Is Involved in Crosstalk between Cartilage and FLS in Collagen-Induced Arthritis. Mediators Inflamm 2020;2020:6473858.
                doi: 10.1155/2020/6473858pubmed: 32908452google scholar: lookup
              5. Arvayo AL, Imbrie-Moore A, Levenston ME. Rapid and durable photochemical bonding of cartilage using the porphyrin photosensitizer verteporfin. Osteoarthritis Cartilage 2019 Oct;27(10):1537-1544.
                doi: 10.1016/j.joca.2019.05.022pubmed: 31229683google scholar: lookup
              6. 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
              7. Matsiko A, Levingstone TJ, O'Brien FJ. Advanced Strategies for Articular Cartilage Defect Repair. Materials (Basel) 2013 Feb 22;6(2):637-668.
                doi: 10.3390/ma6020637pubmed: 28809332google scholar: lookup
              8. Shi S, Man Z, Li W, Sun S, Zhang W. Silencing of Wnt5a prevents interleukin-1β-induced collagen type II degradation in rat chondrocytes. Exp Ther Med 2016 Nov;12(5):3161-3166.
                doi: 10.3892/etm.2016.3788pubmed: 27882132google scholar: lookup
              9. 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
              10. 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
              11. 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
              12. Evans CH, Huard J. Gene therapy approaches to regenerating the musculoskeletal system. Nat Rev Rheumatol 2015 Apr;11(4):234-42.
                doi: 10.1038/nrrheum.2015.28pubmed: 25776949google scholar: lookup
              13. Zhao R, Peng X, Li Q, Song W. Effects of phosphorylatable short peptide-conjugated chitosan-mediated IL-1Ra and igf-1 gene transfer on articular cartilage defects in rabbits. PLoS One 2014;9(11):e112284.
                doi: 10.1371/journal.pone.0112284pubmed: 25390659google scholar: lookup
              14. 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
              15. Saha AK, Kohles SS. A cell-matrix model of anabolic and catabolic dynamics during cartilage biomolecule regulation. Int J Comput Healthc 2012 Jan 1;1(3):214-228.
                doi: 10.1504/IJCIH.2012.046995pubmed: 23795207google scholar: lookup
              16. Santangelo KS, Nuovo GJ, Bertone AL. In vivo reduction or blockade of interleukin-1β in primary osteoarthritis influences expression of mediators implicated in pathogenesis. Osteoarthritis Cartilage 2012 Dec;20(12):1610-8.
                doi: 10.1016/j.joca.2012.08.011pubmed: 22935786google scholar: lookup
              17. 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
              18. 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
              19. Santangelo KS, Bertone AL. Effective reduction of the interleukin-1β transcript in osteoarthritis-prone guinea pig chondrocytes via short hairpin RNA mediated RNA interference influences gene expression of mediators implicated in disease pathogenesis. Osteoarthritis Cartilage 2011 Dec;19(12):1449-57.
                doi: 10.1016/j.joca.2011.09.004pubmed: 21945742google scholar: lookup
              20. Saha AK, Liang Y, Kohles SS. Biokinetic Mechanisms Linked With Musculoskeletal Health Disparities: Stochastic Models Applying Tikhonov's Theorem to Biomolecule Homeostasis. J Nanotechnol Eng Med 2011 May 1;2(2):21004-21012.
                doi: 10.1115/1.4003876pubmed: 21743831google scholar: lookup
              21. Madry H, Cucchiarini M. Clinical potential and challenges of using genetically modified cells for articular cartilage repair. Croat Med J 2011 Jun;52(3):245-61.
                doi: 10.3325/cmj.2011.52.245pubmed: 21674822google scholar: lookup
              22. Pallotta RC, Bjordal JM, Frigo L, Leal Junior EC, Teixeira S, Marcos RL, Ramos L, Messias Fde M, Lopes-Martins RA. Infrared (810-nm) low-level laser therapy on rat experimental knee inflammation. Lasers Med Sci 2012 Jan;27(1):71-8.
                doi: 10.1007/s10103-011-0906-1pubmed: 21484455google scholar: lookup
              23. Saha AK, Kohles SS. Periodic Nanomechanical Stimulation in a Biokinetics Model Identifying Anabolic and Catabolic Pathways Associated With Cartilage Matrix Homeostasis. J Nanotechnol Eng Med 2010 Nov 1;1(4).
                doi: 10.1115/1.4002461pubmed: 21152382google scholar: lookup
              24. Saha AK, Kohles SS. A Distinct Catabolic to Anabolic Threshold Due to Single-Cell Static Nanomechanical Stimulation in a Cartilage Biokinetics Model. J Nanotechnol Eng Med 2010 Aug 1;1(3).
                doi: 10.1115/1.4001934pubmed: 21152243google scholar: lookup
              25. 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
              26. van Osch GJ, Brittberg M, Dennis JE, Bastiaansen-Jenniskens YM, Erben RG, Konttinen YT, Luyten FP. Cartilage repair: past and future--lessons for regenerative medicine. J Cell Mol Med 2009 May;13(5):792-810.
                doi: 10.1111/j.1582-4934.2009.00789.xpubmed: 19453519google scholar: lookup
              27. 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
              28. Wehling N, Palmer GD, Pilapil C, Liu F, Wells JW, Müller PE, Evans CH, Porter RM. Interleukin-1beta and tumor necrosis factor alpha inhibit chondrogenesis by human mesenchymal stem cells through NF-kappaB-dependent pathways. Arthritis Rheum 2009 Mar;60(3):801-12.
                doi: 10.1002/art.24352pubmed: 19248089google scholar: lookup
              29. 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
              30. 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
              31. Mehta K, Gala J, Bhasale S, Naik S, Modak M, Thakur H, Deo N, Miller MJ. Comparison of glucosamine sulfate and a polyherbal supplement for the relief of osteoarthritis of the knee: a randomized controlled trial [ISRCTN25438351]. BMC Complement Altern Med 2007 Oct 31;7:34.
                doi: 10.1186/1472-6882-7-34pubmed: 17974032google scholar: lookup
              32. Miller MJ, Bobrowski P, Shukla M, Gupta K, Haqqi TM. Chondroprotective effects of a proanthocyanidin rich Amazonian genonutrient reflects direct inhibition of matrix metalloproteinases and upregulation of IGF-1 production by human chondrocytes. J Inflamm (Lond) 2007 Aug 14;4:16.
                doi: 10.1186/1476-9255-4-16pubmed: 17697350google scholar: lookup
              33. Steinert AF, Ghivizzani SC, Rethwilm A, Tuan RS, Evans CH, Nöth U. Major biological obstacles for persistent cell-based regeneration of articular cartilage. Arthritis Res Ther 2007;9(3):213.
                doi: 10.1186/ar2195pubmed: 17561986google scholar: lookup
              34. 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
              35. Miller MJ, Ahmed S, Bobrowski P, Haqqi TM. The chrondoprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the presence of IL-1beta. BMC Complement Altern Med 2006 Apr 7;6:13.
                doi: 10.1186/1472-6882-6-13pubmed: 16603065google scholar: lookup
              36. Elkhenany HA, Linardi RL, Ortved KF. Differential modulation of inflammatory cytokines by recombinant IL-10 in IL-1β and TNF-α ̶ stimulated equine chondrocytes and synoviocytes: impact of washing and timing on cytokine responses. BMC Vet Res 2024 Dec 2;20(1):546.
                doi: 10.1186/s12917-024-04403-2pubmed: 39623412google scholar: lookup
              37. Budhiparama NC, Putramega D, Lumban-Gaol I. Orthobiologics in knee osteoarthritis, dream or reality?. Arch Orthop Trauma Surg 2024 Sep;144(9):3937-3946.
                doi: 10.1007/s00402-024-05310-9pubmed: 38630251google scholar: lookup
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