Skip to main content
SpringerLink
Log in

Animal models of arthritis generated by gene transfer

  • Chapter
Gene Therapy in Inflammatory Diseases

Part of the book series: Progress in Inflammation Research ((PIR))

  • 80 Accesses

Abstract

Rheumatoid arthritis (RA) is a crippling autoimmune disease whose primary symptom is chronic inflammation of the joints. Although considered to be a systemic disorder, the most commonly affected sites are the wrist, knees and metacarpophalangeal joints. The debilitating effects of the disease occur progressively over time. The synovium, normally a thin layer of tissue that lines the internal surfaces of the joint capsule, becomes dramatically thickened and hypercellular from infiltrating leukocytes and proliferating synovial cells. The cells within the synovium become activated, giving the hypertrophied tissue an aggressive phenotype. This activated tissue, called pannus, invades and erodes the articular cartilage and subchondral bone. The cumulative degradation of the joint structures often results in severe disfigurement and loss of function. Currently, there is no available treatment that can effectively halt the progression of RA.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Duff GW (1994) Cytokines and acute phase proteins in rheumatoid arthritis. Scand J Rheumatol Suppl 100: 9–19

    Article  PubMed  CAS  Google Scholar 

  2. Mauviel A (1993) Cytokine regulation of metalloproteinase gene expression. J Cell Biochem 53: 288–295

    Article  PubMed  CAS  Google Scholar 

  3. Evans CH, Stefanovic-Racic M, Lancaster J (1995) Nitric oxide and its role in orthopaedic disease. Clin Orthop 312: 275–294

    PubMed  Google Scholar 

  4. Henderson B, Pettipher ER (1989) Arthritogenic actions of recombinant IL-1 and tumour necrosis factor in the rabbit: evidence for synergistic interactions between cytokines in vivo. Clin Exp Immunol 75: 306–310

    PubMed  CAS  Google Scholar 

  5. Pettipher ER, Higgs GA, Henderson B (1986) Interleukin-1 induces leukocyte infiltration and cartilage proteoglycan degradation in the synovial joint. Proc Natl Acad Sci USA 83: 8749–8753

    Article  PubMed  CAS  Google Scholar 

  6. Dingle JT, Thomas DP, King B, Bard DR (1987) In vivo studies of articular tissue damage mediated by catabolin/interleukin-1. Ann Rheum Dis 46: 527–532

    Article  PubMed  CAS  Google Scholar 

  7. Feige U, Karbowski C (1989) Arthritis induced by continuous infusion of hr-interleukin-1 alpha into the rabbit knee-joint. Int J Tissue React 11: 225

    PubMed  CAS  Google Scholar 

  8. Otani K, Nita I, Macaulay W, Georgescu HI, Robbins PD, Evans CH (1996) Suppression of antigen-induced arthritis in rabbits by ex vivo gene therapy. J Immunol 156: 3558–3562

    PubMed  CAS  Google Scholar 

  9. Ghivizzani SC, Lechman ER, Kang R, Tio C, Kolls J, Evans CH, Robbins PD (1998) Direct adenoviral-mediated gene transfer of IL-1 and TNF alpha soluble receptors to rabbit knees with experimental arthritis has local and distal anti-arthritis effects. Proc Natl Acad Sci USA 95: 4613–4618

    Article  PubMed  CAS  Google Scholar 

  10. Evans CH, Robbins PD, Ghivizzani SC, Herndon JH, Kang R (1996) Clinical trial to assess the safety, feasibility, and efficacy of transferring a potentially antiarthritic cytokine gene to human joints with rheumatoid arthritis. Hum Gene Ther 7: 1261–1280

    Article  PubMed  CAS  Google Scholar 

  11. Ghivizzani SC, Kang R, Georgescu HI, Nita I, Jaffurs D, Engle JM, Watkins SC, Tindal MH, Suchanek MK, McKenzie LR, et al. (1997) Constitutive intraarticular expression of human IL-1B following gene transfer to rabbit synovium produces all major pathologies of human arthritis. J Immunol 59: 3604–3

    Google Scholar 

  12. Dinarello CA (1994) The interleukin-1 family: 10 years of discovery. FASEB J 8: 1314–1325

    PubMed  CAS  Google Scholar 

  13. Robbins PD, Thara H, Mueller GM, Hung G, Bahnson A, Zitvogel L, Galea-Lauri J, Ohashi T, Patrene K, Boggs S et al (1994) Retroviral vectors for use in human gene therapy for cancer, Gaucher disease, and arthritis. Ann NY Acad Sci 716: 72–

    Article  PubMed  CAS  Google Scholar 

  14. Ghattas IR, Sanes JR, Majors JE (1991) The encephalomyocarditis virus internal ribosome entry site allows efficient coexpression of two genes from a recombinant provirus in cultured cells and embryos. Mol Cell Biol 11: 5848–5859

    PubMed  CAS  Google Scholar 

  15. Georgescu HI, Mendelow D, Evans CH (1988) HIG-82: an established cell line from rabbit periarticular soft tissue which retains the “activatable” phenotype. In Vitro 24: 1015–1022

    CAS  Google Scholar 

  16. Bandara G, Mueller GM, Galea-Lauri J, Tindal MH, Georgescu HI, Suchanek MK, Hung GL, Glorioso JC, Robbins PD, Evans CH (1993) Intraarticular expression of biologically active interleukin-1-receptor antagonist protein by ex vivo gene transfer. Proc Natl Acad Sci USA 90: 10764–10768

    Article  PubMed  CAS  Google Scholar 

  17. Feldmann M, Brennan FM, Maini RN (1996) The role of cytokines in rheumatoid arthritis. Ann Rev Immunol 14: 397–440

    Article  CAS  Google Scholar 

  18. Roessler BJ, Allen ED, Wilson JM, Hartman JW, Davidson BL (1993) Adenoviral-mediated gene transfer to rabbit synovium in vivo. J Clin Invest 92: 1085–1092

    Article  PubMed  CAS  Google Scholar 

  19. Nita I, Ghivizzani SC, Galea-Lauri J, Bandara G, Georgescu HI, Robbins PD, Evans CH (1996) Direct gene delivery to synovium: an evaluation of potential vectors in vitro and in vivo. Arthritis Rheum 39: 820–828

    Article  PubMed  CAS  Google Scholar 

  20. Yang Y, Nunes FA, Berensci K, Furth EE, Bonczol E, Wilson JM (1994) Cellular immunity to viral antigen limits E1-deleted adenoviruses for gene therapy. Proc Natl Acad Sci USA 91: 4407–4411

    Article  PubMed  CAS  Google Scholar 

  21. Torti FM, Torti SV, Larrick JW, Ringold GM (1989) Modulation of adipocyte differentiation by tumor necrosis factor and transforming growth factor beta. J Cell Biol 108: 1105–1113

    Article  PubMed  CAS  Google Scholar 

  22. Husmann I, Soulet L, Gautron J, Martelly I, Barritault D (1996) Growth factors in skeletal muscle regeneration. Cytokine Growth Factor Rev 7: 249–258

    Article  PubMed  CAS  Google Scholar 

  23. Hayashi S, Gimble JM, Henley A, Ellingsworth LR, Kincade PW (1989) Differential effects of TGF-beta 1 on lymphohemopoiesis in long-term bone marrow cultures. Blood 74: 1711–1717

    PubMed  CAS  Google Scholar 

  24. Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU (1998) In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. Exp Cell Res 238: 265–272

    Article  PubMed  CAS  Google Scholar 

  25. Hall BK, Miyake T (1995) Divide, accumulate, differentiate: cell condensation in skeletal development revisited. Int J Dev Biol 39: 881–893

    PubMed  CAS  Google Scholar 

  26. Fava RA, Olsen N, Keski-Oja J, Moses HL, Pincus T (1989) Active and latent forms of transforming growth factor beta activity in synovial effusions. J Exp Med 169: 291–296

    Article  PubMed  CAS  Google Scholar 

  27. Chu CQ, Field M, Abney E, Zheng RQH, Allard S, Feldmann M, Maini RN (1991) Transforming growth factor-beta 1 in rheumatoid synovial membrane and cartilage/pannus junction. Clin Exp Immunol 86: 380–386

    Article  PubMed  CAS  Google Scholar 

  28. Collier S, Ghosh P (1995) Effects of transforming growth factor beta on proteoglycan synthesis by cell and explant cultures derived from the knee joint meniscus. Osteoarthritis Cartilage 3: 127–138

    Article  PubMed  CAS  Google Scholar 

  29. Allen JB, Manthey CL, Hand AR, Ohura K, Ellingsworth L, Wahl SM (1990) Rapid onset of synovial inflammation and hyperplasia induced by transforming growth factor beta. J Exp Med 171: 231–247

    Article  PubMed  CAS  Google Scholar 

  30. Cooper WO, Fava RA, Gates CO, Cremer MA, Townes AS (1992) Acceleration of onset of collagen-induced arthritis by intra-articular injection of tumour necrosis factor or transforming growth factor-beta. Clin Exp Immunol 89: 244–250

    Article  PubMed  CAS  Google Scholar 

  31. Hartsough MT, Mulder KM (1997) Transforming growth factor-beta signaling in epithelial cells. Pharmacol Ther 75: 21–41

    Article  PubMed  CAS  Google Scholar 

  32. Song XY, Gu M, Jin WW, Klinman DM, Wahl SM (1998) Plasmid DNA encoding transforming growth factor-beta1 suppresses chronic disease in a streptococcal cell wall-induced arthritis model. J Clin Invest 101: 2615–2621

    Article  PubMed  CAS  Google Scholar 

  33. Chernajovsky Y, Adams G, Triantaphyllopoulos K, Ledda MF, Podhajcer OL (1997) Pathogenic lymphoid cells engineered to express TGF-beta 1 ameliorate disease in a collagen-induced arthritis model. Gene Ther 4: 553–559

    Article  PubMed  CAS  Google Scholar 

  34. Nussler AK, Billiar TR (1993) Inflammation, immunoregulation, and inducible nitric oxide synthase. J Leukoc Biol 54: 171–178

    PubMed  CAS  Google Scholar 

  35. Gellar DA, Billiar TR (1998) Molecular biology of nitric oxide synthases. Cancer Metastasis Rev 17: 7–23

    Article  Google Scholar 

  36. Knowles RG, Moncada S (1994) Nitric oxide synthases in mammals. Biochem J 298: 249–258

    PubMed  CAS  Google Scholar 

  37. Farrell AJ, Blake DR, Palmer RM, Moncada S (1992) Increased concentrations of nitrite in synovial fluid and serum samples suggest increased nitric oxide synthesis in rheumatic diseases. Ann Rheum Dis 51: 1219–1222

    Article  PubMed  CAS  Google Scholar 

  38. Ueki Y, Miyake S, Tominaga Y, Eguchi K (1996) Increased nitric oxide levels in patients with rheumatoid arthritis. J Rheumatol 23: 230–236

    PubMed  CAS  Google Scholar 

  39. Grabowski PS, England AJ, Dykhuizen R, Copland M, Benjamin N, Reid DM, Ralston SH (1996) Elevated nitric oxide production in rheumatoid arthritis. Detection using the fasting urinary nitratexreatinine ratio. Arthritis Rheum 39: 643–647

    Article  PubMed  CAS  Google Scholar 

  40. Stefanovic-Racic M, Meyers K, Meschter C, Coffey JW, Hoffman RA, Evans CH (1994) N-monomethylarginine, an inhibitor of nitric-oxide synthase, suppresses the development of adjuvant arthritis in rats. Arthritis Rheum 37: 1062–1069

    Article  PubMed  CAS  Google Scholar 

  41. McCartney-Francis N, Allen JB, Mizel DE, Albina JE, Xie QW, Nathan CF, Wahl SM (1993) Suppression of arthritis by an inhibitor of nitric oxide synthase. J Exp Med 178: 749–754

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Molecular Orthopaedics, Harvard Medical School, 221 Longwood Avenue, Boston, MA, 02115, USA

    Steven C. Ghivizzani & Christopher H. Evans

  2. Departments of Molecular Genetics and Biochemistry and Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15261, USA

    Eric R. Lechman, Daniel Jaffurs, Zhibao Mi, Richard Kang, Thomas S. Muzzonigro & Paul D. Robbins

Authors
  1. Steven C. Ghivizzani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eric R. Lechman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniel Jaffurs
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zhibao Mi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Richard Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Thomas S. Muzzonigro
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Christopher H. Evans
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Paul D. Robbins
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Center for Molecular Orthopaedics, Harvard Medical School, 221 Longwood Avenue, Room BL 152, Boston, MA, 02115, USA

    Christopher H. Evans

  2. University of Pittsburgh School of Medicine, W1246, Biological Sciences Tower, Pittsburgh, PA, 15261, USA

    Paul D. Robbins

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer Basel AG

About this chapter

Cite this chapter

Ghivizzani, S.C. et al. (2000). Animal models of arthritis generated by gene transfer. In: Evans, C.H., Robbins, P.D. (eds) Gene Therapy in Inflammatory Diseases. Progress in Inflammation Research. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8478-5_13

Download citation

  • DOI: https://doi.org/10.1007/978-3-0348-8478-5_13

  • Publisher Name: Birkhäuser, Basel

  • Print ISBN: 978-3-0348-9584-2

  • Online ISBN: 978-3-0348-8478-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation