Spatial and Temporal Distribution of Growth Factors Receptors in the Callus: Implications for Improvement of Distraction Osteogenesis

Management of bone deficits by distraction osteogenesis is an appreciated but lengthy procedure. To accelerate the consolidation of newly formed distraction callus, an administration of growth factors into the distraction gap has been suggested. Changes in expression of growth factors receptors in the distracted callus during consolidation were studied in order to improve our understanding of the underlying molecular mechanisms and to provide a scientific basis for clinical application of growth factors. In a model of rat bone lengthening the expression of receptors for: vascular endothelial growth factor, transforming growth factor beta1, insulin like growth factor and platelet derived growth factor were evaluated semiquantitatively with immunohistochemistry and quantitatively with real time PCR in various callus zones at zero, one and two weeks of consolidation. Overall growth factors receptors' expression was highest at the beginning of consolidation. It was strongest in the trabecular bone and weakest in the fibrous zone. Transforming growth factor beta receptor 1 was most abundant and vascular endothelial growth factor receptor 1, although scarce, showed the most consistent expression. In contrast to the osteogenic zones, the fibrous zone demonstrated a dramatic loss of the growth factors receptors over time. High growth factors receptors expression shortly after termination of the distraction may warrant the maximal callus' response to injected growth factors. Rapid decline of growth factors receptors in the fibrous zone may imply its decreasing sensitivity to growth factors and, as a consequence, a declining osteogenic potential.