Differential transcriptional expression profiles of juvenile and adult calvarial bone.
BACKGROUND
It has widely been observed that young children are capable of reossifying large calvarial defects, while adults lack this endogenous tissue-engineering capacity. The ability of juvenile animals to regenerate calvarial defects has been investigated in multiple animal models, including mice. In this study, the authors used cDNA microarrays to investigate the expression of osteogenesis-associated genes upstream and downstream of Runx2 in juvenile and adult mouse calvaria.


METHODS
Nonsuture-associated parietal bone discs were harvested from 6-day-old (n = 50) and 60-day-old (n = 35) male CD-1 mice. After separation of the underlying dura mater and overlying pericranium, the calvarial discs were snap-frozen and RNA was extracted from pooled samples of calvaria for microarray analysis. Genes analyzed included cytokines, receptors, and cell-surface and matrix proteins both upstream and downstream of Runx2.


RESULTS
Genes associated with the Runx2 pathway had notably higher levels in the juvenile versus adult calvaria. All genes except for osteocalcin were expressed at least twofold higher in the juvenile calvaria. This pattern was validated with quantitative real-time polymerase chain reaction. In addition, mRNA for potent osteoinductive growth factors was present at higher levels in the juvenile compared with the adult calvaria.


CONCLUSIONS
These findings reflect a genomic environment of active osteoblast differentiation and ossification in the juvenile calvaria compared with the adult "quiescent" calvarial tissue. These data suggest that a decreased osteogenic potential of adult calvarial osteoblasts may, in part, explain the inability of adult animals to heal calvarial defects.
Aalami
Oliver O
OO
Department of Surgery, Stanford University School of Medicine, Stanford, Calif 94305-5148, USA.
Nacamuli
Randall P
RP
Salim
Ali
A
Fong
Kenton D
KD
Lenton
Kelly A
KA
Song
Hanjoon M
HM
Fang
Tony D
TD
Longaker
Michael T
MT
D000367:Age Factors; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D020411:Oligonucleotide Array Sequence Analysis; D010012:Osteogenesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012886:Skull / Q000378:metabolism*; D014158:Transcription, Genetic
D050659:Core Binding Factor Alpha 1 Subunit; D016326:Extracellular Matrix Proteins; C493716:Runx2 protein, mouse