Altered expression of mitochondrial genes in response to fracture in old rats.
BACKGROUND
Old rats require more time for bone to bridge a fracture gap than young rats. To explore possible mitochondrial dysfunction in this delay, we measured levels of mRNA derived from mitochondrial genes in healing fractures of young, adult, and old rats.


METHODS
Diaphyseal femoral fractures were induced in female rats at 6, 26, and 52 weeks of age (young, adult, and old rats, respectively). At baseline, at 3 days, and 1, 2, 4, and 6 weeks after fracture, the fracture site was harvested. Total RNA was extracted, and cRNA was prepared and hybridized to 54 Affymetrix U34A microarrays (2 rats/array and 3 arrays/age/time point).


RESULTS
Radiographic union occurred progressively later with age. Of the 107 mitochondria-related genes reviewed, all 8 located within the mitochondrial DNA and some nuclear genes (of the electron transport chain and tricarboxylic acid cycle) showed a prolonged reduction in gene expression after fracture in the oldest rats, to about half the level of expression detected in young rats at 6 weeks after fracture. The transcript levels of apoptotic genes increased after fracture in rats of all three ages, while the transcript levels of 23 mitochondriarelated genes were largely unaltered after fracture.


CONCLUSIONS
Delayed fracture healing in old rats is associated with reduced mRNA expression of genes forming the mitochondrial energy pathways.
Meyer
Martha H
MH
Orthopaedic Research Laboratory, Cannon Research Center, Carolinas Medical Center, Charlotte, NC 28232-2861, USA.
Meyer
Ralph A
RA
D000367:Age Factors; D000818:Animals; D005260:Female; D005264:Femoral Fractures / Q000235:genetics* / Q000378:metabolism; D017102:Fracture Healing / Q000235:genetics* / Q000502:physiology; D015870:Gene Expression / Q000235:genetics*; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D012333:RNA, Messenger