Growth factor regulation of growth factor production by multiple gene transfer to chondrocytes

Abstract

Of the many classes of molecules regulated by growth factors, growth factors themselves are not well investigated. We tested the hypothesis that combinations of endogenous growth factors interactively regulate the production of other growth factors. Growth factors have therapeutic potential for articular cartilage repair, and gene transfer is a promising approach to growth factor delivery. We tested the hypothesis using adult bovine articular chondrocytes treated with combinations of cDNAs encoding insulin-like growth factor I, bone morphogenetic protein-2 and protein-7, transforming growth factor β1, and fibroblast growth factor 2. We found that these growth factor transgenes regulated each other's growth factor production. This regulation ranged from stimulation to inhibition. Regulation by multiple transgenes was not predictable from the regulatory actions of the individual transgenes. Such interactions may be important for the selection of growth factor genes for cell-based therapies, including articular cartilage repair.

Keywords::

• Insulin-like growth factor I
• fibroblast growth factor 2
• transforming growth factor β1
• bone morphogenetic proteins
• chondrocytes
• gene therapy

Acknowledgements

The authors thank Cathy Summerlot for her assistance in the preparation of the manuscript. The authors did not receive writing assistance.

Declaration of interest : This work was supported by NIH grant AR047702 and the Veterans Administration. The sponsors were not involved in the study design; in the collection, analysis, and interpretation of data; in the writing of the report, or in the decision to submit the article for publication. Stephen B. Trippel serves as a paid consultant to Lilly. The other authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.