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Cartilage. 2015 Oct;6(4):264-72. doi: 10.1177/1947603515578691.

Comparison of Efficacy of Endogenous and Exogenous IGF-I in Stimulating Matrix Production in Neonatal and Mature Chondrocytes.

Author information

1
Department of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
2
Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA ; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
3
Department of Orthopaedic Surgery, Indiana University School of Medicine, Indianapolis, IN, USA.
4
Department of Biomedical Engineering, Cornell University, Ithaca, NY, USA ; Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA.

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 EC50 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.

KEYWORDS:

Cartilage Development; Gene Therapy; Growth Factor; Osteoarthritis

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