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Gene Expression During Fracture Healing in Rats Comparing Intramedullary Fixation to Plate Fixation by DNA Microarray

Objective: This study was designed to compare mRNA gene expression in healing diaphyseal femoral fractures between those injuries treated with intramedullary nails and those treated with internal plate fixation. Design: RNA gene expression was measured at 1 day, 3 days, and 1, 2, 4, and 6 weeks after surgery in the fracture callus of rats randomized to femoral shaft fracture with intramedullary nail fixation, rigid plate fixation, or sham fracture. Setting: AAALAC-accredited vivarium of an independent academic medical center. Animals: Fifty-seven, adult, female, Sprague-Dawley rats at 16 weeks of age. Intervention: Femoral fracture with intramedullary nail fixation, femoral fracture with plate and screw fixation, or sham surgery with no fracture. Main Outcome Measurements: RNA expression for 8700 genes was measured with 19 Affymetrix U34A microarrays. The fracture callus was significantly larger with intramedullary nail fixation than with plate fixation. Most genes responded to fracture with a change in mRNA expression. Most of the responding genes followed the same time course for both fixation methods. This included genes related to growth factors, bone matrix, mast cells, most nerve factors, and hematopoiesis. The intramedullary nail group had significantly greater up-regulation for transcripts related to cartilage, cell division, inflammation, and the acetylcholine receptor. There was significantly greater up-regulation in the plate group for genes related to macrophage activity. Conclusions: There were differentially expressed genes present between the 2 surgical groups that may give insight into the control of fracture repair.