Studying the role of epidermal growth factor in chondrogenesis

Abstract

In the growth plate, chondrocytes go through stages of rest, proliferation and hypertrophy. The hypertrophic chondrocytes are important in synthesis of the extracellular matrix. Our previous study has shown that epidermal growth factor (EGF) is expressed mainly in hypertrophic chondrocytes. Widespread overexpression of EGF in transgenic mice resulted in stunted growth and abnormalities in the growth plate. We therefore hypothesize that EGF may play a role in chondrogenesis. In order to test this, we are generating transgenic mice which overexpress EGF specifically in the proliferative zone of the growth plate. We will employ gene targeting to “knock-in” EGF into the Col9a1 locus which encodes collagen IX. Collagen IX is expressed in the proliferating chondrocytes and heterozygous null mutants are phenotypically normal. The phenotypic consequences of overexpression of EGF in proliferating chondrocytes wil be studied using morphometry and molecular markers.