Frazier Brenda C, Mooney Mark P, Losken H Wolfgang, Barbano Tim, Moursi Amr, Siegel Michael I, Richtsmeier Joan T
Department of Anthropology, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Cleft Palate Craniofac J. 2008 Nov;45(6):571-82. doi: 10.1597/07-095.1. Epub 2007 Dec 31.
Overexpression of transforming growth factor-beta 2 has been associated with craniosynostosis and resynostosis following surgery. We examined the effects of localized transforming growth factor-beta 2 inhibition on craniofacial phenotype in rabbits with craniosynostosis.
Twenty-five New Zealand white rabbits with bilateral coronal craniosynostosis were divided into three treatment groups: (1) suturectomy control (n=8); (2) suturectomy with nonspecific, control immunoglobulin G antibody (n=6); and (3) suturectomy with anti-transforming growth factor-beta 2 antibody (n=11). At 10 days of age, a coronal suturectomy was performed on all rabbits. The sites in groups 2 and 3 were immediately filled with a slow-resorbing collagen gel mixed with either immunoglobulin G or anti-transforming growth factor-beta 2 antibody. Computed tomography scans of each rabbit were acquired at ages 10, 25, and 84 days. Craniofacial landmarks were collected from three-dimensional computed tomography reconstructions, and growth and form were compared among the three groups.
Rabbits treated with anti-transforming growth factor-beta 2 antibody differed in form at 84 days of age compared with suturectomy control rabbits, specifically in the snout and posterior neurocranium. Growth in some areas of the skull was greater in rabbits from the anti-transforming growth factor-beta 2 group than in suturectomy control rabbits, but not significantly greater than in IgG control rabbits.
We find support for the hypothesis that transforming growth factor-beta 2 inhibition alters adult form, but these changes do not appear to be localized to the suturectomy region. Slight differences in form and growth between the two control groups suggest that the presence of the collagen vehicle itself may affect skull growth.
转化生长因子-β2的过表达与颅骨缝早闭及手术后再狭窄有关。我们研究了局部抑制转化生长因子-β2对患有颅骨缝早闭的兔子颅面表型的影响。
25只患有双侧冠状缝颅骨缝早闭的新西兰白兔被分为三个治疗组:(1)缝切除术对照组(n = 8);(2)缝切除术加非特异性对照免疫球蛋白G抗体(n = 6);(3)缝切除术加抗转化生长因子-β2抗体(n = 11)。在10日龄时,对所有兔子进行冠状缝切除术。第2组和第3组的手术部位立即填充与免疫球蛋白G或抗转化生长因子-β2抗体混合的缓慢吸收胶原凝胶。在10、25和84日龄时对每只兔子进行计算机断层扫描。从三维计算机断层扫描重建中收集颅面标志点,并比较三组之间的生长和形态。
与缝切除术对照组兔子相比,用抗转化生长因子-β2抗体治疗的兔子在84日龄时形态不同,特别是在口鼻部和后神经颅骨。抗转化生长因子-β2组兔子颅骨某些区域的生长比缝切除术对照组兔子更大,但并不显著大于免疫球蛋白G对照组兔子。
我们发现支持转化生长因子-β2抑制会改变成年形态这一假设的证据,但这些变化似乎并不局限于缝切除区域。两个对照组在形态和生长上的细微差异表明胶原载体本身的存在可能会影响颅骨生长。