Abstract
BACKGROUNDnAG and Prod-1 are proteins responsible for the regeneration of completely amputated limbs in salamanders (which are lower vertebrates). The purpose of this study was to introduce an experimental distal phalanx amputation model in mice (which are higher vertebrates) in which nAG and Prod-1 are expressed in the amputation stumps. METHODSSixteen mice with amputation of the distal two-thirds of the distal phalanx were used. One hind limb was used and the central three digits were amputated. Injection of nAG and Prod-1 plasmids was performed in the footpad twice weekly in experimental mice (n = 8), and injection of solution only (without the plasmids) was performed twice weekly in control mice (n = 8). RESULTSnAG and Prod-1 were expressed in experimental stumps only. This expression results in quicker and more mature bone regeneration in experimental animals, and this was shown using histology and immune stains to osteocalcin (an osteoblast marker). Finally, quantitative mRNA showed a 21-fold increase of osteocalcin in experimental stumps compared with control stumps, and this was statistically significant. CONCLUSIONInjection of nAG and Prod-1 into the footpad will result in their expression in the distal amputation stumps, and this will enhance bone regeneration in the model described.