Comparison of efficacy of endogenous and exogenous IGF-I in stimulating matrix production in neonatal and mature chondrocytes

Izath N. Aguilar, Stephen Trippel, Shuiliang Shi, Lawrence J. Bonassar

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Objective. The goal of this study was to compare the efficacy of endogenous upregulation of IGF-I by gene therapy and exogenous addition of insulin-like growth factor I (IGF-I) in enhancing proteoglycan synthesis by skeletally mature and neonatal chondrocytes. Chondrocyte transplantation therapy is a common treatment for focal cartilage lesions, with both mature and neonatal chondrocytes used as a cell source. Additionally, gene therapy strategies to upregulate growth factors such as IGF-I have been proposed to augment chondrocyte transplantation therapies. Methods. Both skeletally mature and neonatal chondrocytes were exposed to either an adeno-associated virus-based plasmid containing the IGF-I gene or exogenous IGF-I. Results. Analysis of IGF-I and glycosaminoglycan production using a 4-parameter dose-response model established a clear connection between the amount of IGF-I produced by cells and their biosynthetic response. Both neonatal and mature chondrocytes showed this relationship, but the sensitivities were quite different, with EC50 of 0.57 ng/mL for neonatal chondrocytes and ED50 of 8.70 ng/mL IGF-I for skeletally mature chondrocytes. Conclusions. These data suggest that IGF-I gene therapy may be more effective with younger cell sources. Both cell types were less sensitive to exogenous IGF-I than endogenous IGF-I.

Original languageEnglish (US)
Pages (from-to)264-272
Number of pages9
JournalCartilage
Volume6
Issue number4
DOIs
StatePublished - Jan 1 2015

Keywords

  • Cartilage Development
  • Gene Therapy
  • Growth Factor
  • Osteoarthritis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Biomedical Engineering
  • Physical Therapy, Sports Therapy and Rehabilitation

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