Gene Transfer to Articular Chondrocytes with Recombinant Adenovirus

  • Glyn D. Palmer
  • Elvire Gouze
  • Jean-Noel Gouze
  • Oliver B. Betz
  • Christopher H. Evans
  • Steven C. Ghivizzani
Part of the Methods in Molecular Biology™ book series (MIMB, volume 215)


Articular cartilage forms the load-bearing surfaces of diarthrodial joints. Its dense extracellular matrix, composed primarily of water, collagen, and proteoglycans is maintained by a resident population of chondrocytes. These all combine to form a highly organized structure that provides the tissue with its unique biomechanical properties. However, partly because of its avascular nature, cartilage has poor regenerative properties, and damage from disease or injury will often lead to an inferior repair tissue that ultimately fails. One approach to promoting cartilage repair is through the administration of biological agents that enhance matrix synthesis or decrease matrix degradation. Several cytokines are known to promote matrix synthesis in chondrocytes, including the bone morphogenic proteins (BMPs), transforming growth factor-βs (TGF-βs) and insulinlike growth factors (IGFs). Improved repair has been reported following in vivo administration of recombinant IGF-1 (1) or BMP-2 (2) to cartilage lesions. However, the maintainence of effective intralesional cytokine concentrations for extended periods following administration is hindered by the relatively short half-lives of these proteins. The transfer of cDNAs encoding these cytokines represents an alternative treatment strategy. By this approach, local expression of the gene to cells within sites of damage could achieve sustained, biologically relevant levels of protein that are synthesized locally (3).


Recombinant Adenovirus loxP Site Isoamyl Alcohol Shuttle Plasmid Recombinant Adenoviral Vector 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Nixon, A. J., Saxer, R. A., and Brower-Toland, B. D. (2001) Exogenous insulinlike growth factor-I stimulates an autoinductive IGF-I autocrine/paracrine response in chondrocytes. J. Orthop. Res. 19, 26–32.PubMedCrossRefGoogle Scholar
  2. 2.
    Sellers, R. S., Peluso, D., and Morris, E. A. (1997) The effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the healing of full-thickness defects of articular cartilage. J. Bone Joint Surg. Am. 79, 1452–1463.PubMedGoogle Scholar
  3. 3.
    Evans, C. H., Ghivizzani, S. C., Smith, P., Shuler, F. D., Mi, Z., and Robbins, P. D. (2000) Using gene therapy to protect and restore cartilage. Clin. Orthop. S214–S219.Google Scholar
  4. 4.
    Roessler, B. J., Allen, E. D., Wilson, J. M., Hartman, J. W., and Davidson, B. L. (1993) Adenoviral-mediated gene transfer to rabbit synovium in vivo. J. Clin. Invest. 92, 1085–1092.PubMedCrossRefGoogle Scholar
  5. 5.
    Nita, I., Ghivizzani, S. C., Galea-Lauri, J., Bandara, G., Georgescu, H. I., Robbins, P. D., et al. (1996) Direct gene delivery to synovium. An evaluation of potential vectors in vitro and in vivo. Arthritis Rheum. 39, 820–828.PubMedCrossRefGoogle Scholar
  6. 6.
    Kang, R., Marui, T., Ghivizzani, S. C., Nita, I. M., Georgescu, H. I., Suh, J. K., et al. (1997) Ex vivo gene transfer to chondrocytes in full-thickness articular cartilage defects: a feasibility study. Osteoarthritis Cartilage 5, 139–143.PubMedCrossRefGoogle Scholar
  7. 7.
    Baragi, V. M., Renkiewicz, R. R., Qiu, L., Brammer, D., Riley, J. M., Sigler, R. E., et al. (1997) Transplantation of adenovirally transduced allogeneic chondrocytes into articular cartilage defects in vivo. Osteoarthritis Cartilage 5, 275–282.PubMedCrossRefGoogle Scholar
  8. 8.
    Smith, P., Shuler, F. D., Georgescu, H. I., Ghivizzani, S. C., Johnstone, B., Niyibizi, C., et al. (2000) Genetic enhancement of matrix synthesis by articular chondrocytes: comparison of different growth factor genes in the presence and absence of interleukin-1. Arthritis Rheum. 43, 1156–1164.PubMedCrossRefGoogle Scholar
  9. 9.
    Shuler, F. D., Georgescu, H. I., Niyibizi, C., Studer, R. K., Mi, Z., Johnstone, B., et al. (2000) Increased matrix synthesis following adenoviral transfer of a transforming growth factor beta1 gene into articular chondrocytes. J. Orthop. Res. 18, 585–592.PubMedCrossRefGoogle Scholar
  10. 10.
    Mi, Z., Ghivizzani, S. C., Lechman, E. R., Jaffurs, D., Glorioso, J. C., Evans, C. H., et al. (2000) Adenovirus-mediated gene transfer of insulin-like growth factor 1 stimulates proteoglycan synthesis in rabbit joints. Arthritis Rheum. 43, 2563–2570.PubMedCrossRefGoogle Scholar
  11. 11.
    Hardy, S., Kitamura, M., Harris-Stansil, T., Dai, Y., and Phipps, M. L. (1997) Construction of adenovirus vectors through Cre-lox recombination. J. Virol. 71, 1842–1849.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2003

Authors and Affiliations

  • Glyn D. Palmer
    • 1
  • Elvire Gouze
    • 2
  • Jean-Noel Gouze
    • 1
    • 3
  • Oliver B. Betz
    • 1
  • Christopher H. Evans
    • 1
  • Steven C. Ghivizzani
    • 1
  1. 1.Center for Molecular OrthopaedicsHarvard Medical SchoolBoston
  2. 2.Molecular OrthopedicsHarvard Medical SchoolBoston
  3. 3.Electrical Engineering and Computer Sciences LaboratoryMassachusetts Institute of TechnologyCambridge

Personalised recommendations