Regulation of articular chondrocyte aggrecan and collagen gene expression by multiple growth factor gene transfer

Shuiliang Shi, Scott Mercer, George J. Eckert, Stephen B. Trippel

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Gene transfer is a promising approach to the delivery of chondrotrophic growth factors to promote cartilage repair. It is unlikely that a single growth factor transgene will optimally regulate these cells. The aim of this study was to identify those growth factor transgene combinations that optimally regulate aggrecan, collagen type II and collagen type I gene expression by articular chondrocytes. We delivered combinations of the transgenes encoding fibroblast growth factor-2, insulin-like growth factor I, transforming growth factor beta1, bone morphogenetic protein-2, and/or bone morphogenetic protein-7 and assessed chondrocyte responses by measuring changes in the expression of aggrecan, type II collagen and type I collagen genes. These growth factor transgenes differentially regulated the magnitude and time course of all three-matrix protein genes. In concert, the transgenes regulated matrix gene expression in an interactive fashion that ranged from synergistic to inhibitory. Maximum stimulation of aggrecan (16-fold) and type II collagen (35-fold) expression was with the combination of IGF-I, BMP-2, and BMP-7 transgenes. The results indicate that the optimal choice of growth factor genes for cell-based cartilage repair cannot be predicted from observations of individual transgenes. Rather, such gene therapy will require an empirically based selection of growth factor gene combinations.

Original languageEnglish (US)
Pages (from-to)1026-1031
Number of pages6
JournalJournal of Orthopaedic Research
Volume30
Issue number7
DOIs
StatePublished - Jul 2012

Keywords

  • aggrecan
  • articular chondrocytes
  • collagen
  • gene therapy
  • growth factors

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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