Genes with greater up-regulation in the fracture callus of older rats with delayed healing

The rate of bone formation to bridge a fracture gap slows with age. To explore potential pathogenic mechanisms and possible negative‐feedback responses by the skeleton to this reduced rate of healing, mRNA transcripts up‐regulated more and/or longer were studied in older rats with delayed healing. Female rats at 6 (young), 26 (adult), and 52 (old) weeks of age received unilateral diaphyseal femoral fractures with intramedullary rod stabilization. At 0, 0.4, 1, 2, 4, and 6 weeks after fracture, the fracture site was harvested. Total RNA was extracted, cRNA was prepared, and the cRNA was hybridized to 54 Affymetrix U34A microarrays (three arrays/age/time point). Transcripts for 180 genes were identified as up‐regulated more and/or longer in old rats with delayed fracture healing. Of these, 60 were selected for more intense review. Significantly more and/or longer expression was seen in genes related to myofibroblasts, cell proliferation, calcification inhibition, TGF‐β activity, lipid metabolism, cell adhesion, and the cytoskeleton. Further study is needed to determine if these up‐regulated transcripts are related to the pathological processes which slow healing or are related to attempts by the fracture tissue to stimulate bone to bridge the fracture gap. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:488–494, 2007