Cray James J, Burrows Anne M, Vecchione Lisa, Kinsella Christopher R, Losee Joseph E, Moursi Amr M, Siegel Michael I, Cooper Gregory M, Mooney Mark P
Department of Surgery, Division of Plastic Surgery, Pediatric Craniofacial Biology Laboratory, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Cleft Palate Craniofac J. 2012 Sep;49(5):e46-54. doi: 10.1597/11-024. Epub 2011 Jul 8.
Craniosynostosis affects 1 in 2000 to 3000 live births and may result in craniofacial and neural growth disturbances. Histological data have shown that thick collagenous bundles are present in the sutural ligament, which may tether the osteogenic fronts, resulting in premature fusion. The hormone relaxin has been shown to disrupt collagen fiber organization, possibly preventing craniosynostosis by relaxing the sutural ligament and allowing osteogenic fronts to separate normally and stay patent. This study tested this hypothesis with a rabbit model of delayed-onset coronal suture synostosis.
A total of 18 New Zealand White rabbits with craniosynostosis were randomly assigned to one of three groups: sham control, protein control (BSA), relaxin treatment. After initial diagnosis, sham surgery, BSA, or relaxin was delivered to the fusing coronal suture in a slow-release (56-day) collagen vehicle. Longitudinal radiographs and body weights were collected at 10, 25, 42, and 84 days of age, and sutures were harvested for histology.
Relaxin-treated animals had more disorganized intrasuture content than control groups. These specimens also appeared to have relatively wider sutures ectocranially. There were no significant differences in relaxin-treated animals for all craniofacial growth measures, or suture separation compared with controls.
These data do not support our initial hypothesis that the use of relaxin may rescue sutures destined to undergo premature suture fusion. These findings suggest that collagen fiber arrangement may not be important for suture fusion. This protein therapy would not be clinically useful for craniosynostosis.
颅缝早闭在每2000至3000例活产儿中出现1例，可能导致颅面和神经生长紊乱。组织学数据表明，缝合韧带中存在粗大的胶原束，这可能会束缚成骨前沿，导致过早融合。已证明激素松弛素会破坏胶原纤维结构，可能通过松弛缝合韧带并使成骨前沿正常分离并保持开放来预防颅缝早闭。本研究用延迟发作冠状缝早闭的兔模型验证了这一假设。
总共18只患有颅缝早闭的新西兰白兔被随机分为三组之一：假手术对照组、蛋白质对照组（牛血清白蛋白）、松弛素治疗组。初步诊断后，将假手术、牛血清白蛋白或松弛素以缓释（56天）胶原载体递送至融合的冠状缝。在10、25、42和84日龄时收集纵向X线片和体重，并采集缝合处以进行组织学检查。
接受松弛素治疗的动物的缝合线内成分比对照组更紊乱。这些标本在颅外也似乎有相对更宽的缝线。与对照组相比，接受松弛素治疗的动物在所有颅面生长指标或缝线分离方面均无显著差异。
这些数据不支持我们最初的假设，即使用松弛素可能挽救注定要过早缝合融合的缝线。这些发现表明胶原纤维排列可能对缝线融合并不重要。这种蛋白质疗法对颅缝早闭在临床上并无用处。
