DAMD 17 - 02 - 1 - 0685 TITLE : Gene Therapy for Fracture Repair

Microarray analysis of gene expression was performed in the healing femur fractures of 13-week-old male rats during the inflammatory stageof repair, at 3 days post-fracture, and the endochondral bone formation stage of repair, at 11 days post-fracture. Multiple replicate pairs of fracturetissues paired with unfractured tissues, and unfractured control bones that had the stabilizing K-wire were introduced. This approach normalizedthe marrow contributions to the RNA repertoire. We identified 6555 genes with significant changes in expression in fracture tissues at 3 days and11 days healing. The repertoire of growth factor genes expressed was also surprisingly restricted at both post-fracture intervals. The large numberof Expressed Sequence Tags (ESTs) expressed at both post-fracture times indicates that several molecular pathways yet to be identified regulatefracture repair. The number of genes expressed during immune responses and inflammatory processes was restricted with higher expressionlargely during the early post-fracture analysis. Several of the genes identified in this study have been associated with regulation of cell andextracellular matrix interactions during scarless healing of fetal skin wounds. These observations suggest that these genes might also regulate thescarless healing characteristic of bone regeneration by similar mechanisms.© 2005 Elsevier Inc. All rights reserved.