AGE ALTERS mRNA GENE EXPRESSION IN THE FRACTURE CALLUSOF RATS BY MICROARRAY ANALYSIS

INTRODUCTION: The time required for bridging callus formation following femoral fracture increases with age in the rat (1). While young, 6-week-old rats form bridging callus by 4 weeks after fracture, adult, 26-week-old rats require 10 weeks, and older, 52-week-old rats need in excess of 26 weeks (1). Despite this increased time to healing with age, there was no increase in the time of expression of Indian hedgehog or any of the bone morphogenetic proteins in the fracture callus (2). Bridging callus formation for adult and older rats occurred after the time of expression of these skeletally active cytokines (2). Except for markers of osteoblast activity and bone matrix formation, few genes remain up-regulated in the time period of bridging callus formation (3). These earlier studies revealed a paucity of data for genes differentially expressed by age. Either bridging callus formation is not subject to negative-feedback control, or the genes up-regulated to control bridging callus formation are not those normally thought of as being involved in skeletal homeostasis. This suggested the need for a wider search for genes active during the fracture reparative process. In this project, mRNA gene expression was measured by DNA microarray technology at various time points for young, adult, and older rats. The goal was to identify genes whose expression following fracture was altered by age. Such genes may be involved in fracture healing, either by causing the slowing with age by loss of function, or by responding to the slowing with enhanced gene expression to attempt to accelerate the healing process.