IGF-1 gene therapy to protect articular cartilage in a rat model of joint damage

Iñigo Izal, Carlos Alberto Acosta, Purificación Ripalda, Mikel Zaratiegui, Juan Ruiz, Francisco Forriol

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Introduction: An adeno-associated virus (AAV) derived vector in gene transfer model that induces IGF-1 expression could repair articular cartilage. Materials and methods: Male Wistar rats, 150 and 200 g, and 7 weeks old, were used. Effectiveness of constructed vectors was assayed inoculating them in rat knees of control and damaged animals either mechanically or by collagen-induced arthritis. Inoculation was intra-articular with 50 μL of recombinant AAV-Luciferase (1.25 × 108 particles). The rats were killed after 1, 2, 4 and 8 weeks. IGF-I activity was analyzed by injecting 50 μL of recombinant AAV (1.25 × 108 particles) in animals with damaged knees. Final analysis was performed after 8 weeks. Results: The activity of AAV vectors in vitro shows the presence of mRNA coding to IGF-I in cells infected with AAV-IGF and not in control cells without viral vectors and an increase in secreted IGF-I protein in culture medium. In vivo, AAV derived vectors induced protein expression in cartilage 2 months after inoculation. In the animals killed after 1 and 2 weeks, no significant increase in the reaction of luciferase was observed (P > 0.05). In the group of animals with no injury an increase was observed at 4 weeks, which was more marked and significant after 8 weeks (P = 0.029). The same behavior occurred in the animals with induced arthritis and in the mechanical injury group. In the levels of expression after 8 weeks, no significant differences were found between the two groups of injured animals and the group of healthy animals infected with the virus. The joints of the animals that were subjected to injuries in the cartilage and inoculated with AAV-IGF-I presented a similar appearance to those animals inoculated with saline solution. Conclusion: Autoimmune and mechanical lesions did not show improvement in the state of its cartilage after the treatment. The use of AAV vectors capable of inducing the expression of IGF-I in vitro is therefore not sufficient to protect the cartilage from the serious damage.

Original languageEnglish (US)
Pages (from-to)239-247
Number of pages9
JournalArchives of Orthopaedic and Trauma Surgery
Volume128
Issue number2
DOIs
StatePublished - Feb 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Surgery
  • Orthopedics and Sports Medicine

Keywords

  • Adeno-associated virus
  • Arthritis
  • Cartilage
  • Gene therapy
  • IGF-I

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