The effectof age on gene expression in adult and juvenile rats following femoral fracture

Objective: To compare mRNA gene expression during fracture healing in young and adult rats. Design: Gene expression was measured at zero, 1, 2, 4, 6, 8 and 10 weeks after fracture (6 rats/age/time point) in rats at 6 and 26 weeks of age at surgery. Setting: AAALAC-accredited vivarium of an independent academic medical center. Animals: Female Sprague-Dawley rats at 6 and 26 weeks of age. Intervention: An intramedullary rod was placed retrograde in the left femur, and a simple transverse closed middiaphyseal fracture was induced. Main Outcome Measurements: mRNA gene expression was measured for 34 genes for extracellular matrix, osteoblasts, bone morphogenic protein, inflammation, cytokine, and receptor genes. Results: The young rats reached radiographic union by 4 weeks after fracture, whereas the adult rats took 8 to 10 weeks to unite. All genes studied increased in mRNA expression with a peak at 1 to 2 weeks after fracture. All genes in the young rats then subsided to baseline by 4 weeks after fracture. However, during the longer period needed for radiographic union in the adult rats, only genes related to bone matrix, osteoblastic markers, angiogenesis, and the fibroblast growth factors remained significantly up-regulated at 4 and 6 weeks after fracture. Genes related to cartilage, Indian hedgehog, the bone morphogenctic proteins, and transforming growth factor-beta came to undetectable baseline values in the adult rats prior to radiographic union. Conclusions: Most stimulators of bone healing are not expressed during the later stages of fracture repair in adult rats. Other genes must control bone growth to bridge the fracture gap.