Altered mRNA expression of genes related to nerve cell activity in the fracture callus of older rats: A randomized, controlled, microarray study.
BACKGROUND
The time required for radiographic union following femoral fracture increases with age in both humans and rats for unknown reasons. Since abnormalities in fracture innervation will slow skeletal healing, we explored whether abnormal mRNA expression of genes related to nerve cell activity in the older rats was associated with the slowing of skeletal repair.


METHODS
Simple, transverse, mid-shaft, femoral fractures with intramedullary rod fixation were induced in anaesthetized female Sprague-Dawley rats at 6, 26, and 52 weeks of age. At 0, 0.4, 1, 2, 4, and 6 weeks after fracture, a bony segment, one-third the length of the femur, centered on the fracture site, including the external callus, cortical bone, and marrow elements, was harvested. cRNA was prepared and hybridized to 54 Affymetrix U34A microarrays (3/age/time point).


RESULTS
The mRNA levels of 62 genes related to neural function were affected by fracture. Of the total, 38 genes were altered by fracture to a similar extent at the three ages. In contrast, eight neural genes showed prolonged down-regulation in the older rats compared to the more rapid return to pre-fracture levels in younger rats. Seven genes were up-regulated by fracture more in the younger rats than in the older rats, while nine genes were up-regulated more in the older rats than in the younger.


CONCLUSIONS
mRNA of 24 nerve-related genes responded differently to fracture in older rats compared to young rats. This differential expression may reflect altered cell function at the fracture site that may be causally related to the slowing of fracture healing with age or may be an effect of the delayed healing.
Department of Orthopaedic Surgery, Carolinas Medical Center, Charlotte, NC 28232-2861 USA. mmeyer@carolinas.org
Martha H
MH
Meyer
Wiguins
W
Etienne
Ralph A
RA
Meyer
D000375:Aging / Q000235:genetics; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D002146:Bony Callus / Q000378:metabolism*; D005260:Female; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D005269:Femur / Q000294:innervation; D005593:Fracture Fixation, Internal; D017102:Fracture Healing / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D009416:Nerve Regeneration / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010525:Peripheral Nerves / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D011859:Radiography; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger