Quantitative assessment of cranial defect healing and correlation with the expression of TGF-beta.
Circular parietal defects from 3 to 12 mm in diameter were made in 45 6-month old skeletally mature guinea pigs, and animals were sacrificed after survival periods of 3 days to 12 weeks. The original defect was harvested in continuity with a rim of surrounding bone and the adjacent dura and pericranium. After 12 weeks, all 3 and 5 mm defects were completely covered by a bridge of bone, while residual defects were noted within the 8 and 12 mm wounds. Percentage of new bone formation was significantly higher within 3 mm defects, than in all larger defects at each time interval from 1 week on (P < .05), reaching a mean of 93% in 3 mm defects and remaining below a mean of 31% in the remaining defect sizes. Immunolocalization demonstrated an osteogenic front in which the osteoblasts stained strongly for all isoforms of TGF-beta, with the intensity decreasing after the majority of the defects had reossified; this front was located at the advancing bone edge of the defect as well as the endocranial side adjacent to the dura. In conclusion, isoforms of TGF-beta are upregulated during a limited "window" of time corresponding to the period of calvarial reossification, and are localized to osteoblasts within an osteogenic front at the periphery and dural surfaces of the defects.
Gosain
A K
AK
Department of Plastic and Reconstructive Surgery, Medical College of Wisconsin, Milwaukee, USA. agosain@mcw.edu
Song
L
L
Yu
P
P
Mehrara
B J
BJ
Maeda
C Y
CY
Gold
L I
LI
Longaker
M T
MT
D000818:Animals; D001861:Bone Regeneration / Q000502:physiology*; D015870:Gene Expression; D006168:Guinea Pigs; D007150:Immunohistochemistry; D008297:Male; D020033:Protein Isoforms; D012886:Skull / Q000293:injuries*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation; D014945:Wound Healing / Q000502:physiology*
D020033:Protein Isoforms; D016212:Transforming Growth Factor beta