title: Quantitative assessment of cranial defect healing and correlation with the expression of TGF-beta.
abstract: 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.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Medical College of Wisconsin, Milwaukee, USA. agosain@mcw.edu
authors.forename: A K
authors.initials: AK
authors.lastname: Gosain
authors.forename: L
authors.initials: L
authors.lastname: Song
authors.forename: P
authors.initials: P
authors.lastname: Yu
authors.forename: B J
authors.initials: BJ
authors.lastname: Mehrara
authors.forename: C Y
authors.initials: CY
authors.lastname: Maeda
authors.forename: L I
authors.initials: LI
authors.lastname: Gold
authors.forename: M T
authors.initials: MT
authors.lastname: Longaker
mesh_terms: 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*
chemical_list: D020033:Protein Isoforms; D016212:Transforming Growth Factor beta