Yu J C, McClintock J S, Gannon F, Gao X X, Mobasser J P, Sharawy M
Division of Plastic Surgery, Medical College of Georgia, Augusta 30912-4080, USA.
Plast Reconstr Surg. 1997 Jul;100(1):23-31. doi: 10.1097/00006534-199707000-00005.
Dura plays an important role in calvarial morphogenesis. However, precisely what that role is remains unclear. We present here in vivo evidence that dura without other central nervous system components induces both chondrogenesis and osteogenesis. The mechanism is, at least in part, by proximate tissue interaction. The objectives of this experiment were to answer the following: (1) Can dura actually induce osteogenesis without the influence of the underlying brain? (2) What are the requirements of this dura-induced heterotopic osteogenesis? (3) What are the differences between dura underlying sutures and dura underlying the squamous portions of the cranial bones? Dura underlying the metopic, sagittal, and lambdoidal sutures and dura underlying the flat portions of frontal and parietal bones were obtained from neonatal Lewis rats and transplanted into the posterior thoraces of adult Lewis recipients. In group I, dura underlying the metopic, sagittal, and lambdoidal sutures (n = 20) and dura underlying the flat portions of frontal and parietal bones (n = 20) were transplanted individually into separate epitheliomesenchymal pockets. Group II animals had dura underlying the metopic, sagittal, and lambdoidal sutures (n = 10) and dura underlying the flat portions of frontal and parietal bones (n = 10) transplanted individually into surgically created mesenchymal pockets by placing the dura grafts between panniculus carnosus and latissimus dorsi muscles. The animals were sacrificed at 2-week intervals. Light microscopy, special histochemical analysis, immunohistochemistry, and electron microscopy were performed. Bone formation was seen in 15 of the 18 animals (83 percent) in group I. No bone or cartilage formation was seen in group II. Chondrogenesis was seen in 4 animals receiving dura underlying the metopic, sagittal, and lambdoidal sutures in group I. Cellular hyperproliferation was seen at 2 weeks when dura was transplanted close to the hair follicles. These cells had a high nucleus-to-cytoplasm ratio and were positive for transforming growth factor beta. This hyperproliferation was followed by production and accumulation of Alcian blue-positive extracellular matrix that resisted digestion by hyaluronidase. Cellularly active cartilage was seen at 6 weeks. There was no chondrogenesis in animals receiving dura underlying the flat portions of frontal and parietal bones in group I. Electron microscopy demonstrated the presence of proteoglycan-like ground substance and type II collagen in the inner layer of sutural dura and the predominance of dense type I collagen in the squamous dura and the external layer of the sutural dura. The important findings of this experiment are that (1) heterotopically transplanted neonatal dura can induce osteogenesis, (2) this heterotopic osteoinduction by dura requires epitheliomesenchymal interaction, and (3) separating dura into sutural dura and squamous dura, chondrogenesis occasionally occurred in addition to osteogenesis with the former, while only membranous ossification occurred with the latter, indicating intrinsic differences within the dura mater. This dural heterogeneity is supported by direct ultrastructural data.
硬脑膜在颅骨形态发生中起重要作用。然而,其具体作用仍不清楚。我们在此提供体内证据表明,没有其他中枢神经系统成分的硬脑膜可诱导软骨生成和成骨。其机制至少部分是通过邻近组织相互作用。本实验的目的是回答以下问题:(1)硬脑膜在无其下方脑的影响下能否实际诱导成骨?(2)这种硬脑膜诱导的异位成骨需要哪些条件?(3)缝合处下方的硬脑膜与颅骨鳞状部分下方的硬脑膜有何差异?从新生Lewis大鼠获取额缝、矢状缝和人字缝下方的硬脑膜以及额骨和顶骨平坦部分下方的硬脑膜,并将其移植到成年Lewis受体的后胸部。在第一组中,将额缝、矢状缝和人字缝下方的硬脑膜(n = 20)以及额骨和顶骨平坦部分下方的硬脑膜(n = 20)分别移植到单独的上皮间充质袋中。第二组动物将额缝、矢状缝和人字缝下方的硬脑膜(n = 10)以及额骨和顶骨平坦部分下方的硬脑膜(n = 10)分别通过将硬脑膜移植物置于颈阔肌和背阔肌之间移植到手术创建的间充质袋中。每隔2周处死动物。进行了光学显微镜检查、特殊组织化学分析、免疫组织化学和电子显微镜检查。第一组18只动物中有15只(83%)出现骨形成。第二组未见骨或软骨形成。在第一组接受额缝、矢状缝和人字缝下方硬脑膜的4只动物中出现软骨生成。当硬脑膜移植靠近毛囊时,在2周时可见细胞过度增殖。这些细胞核质比高,转化生长因子β呈阳性。这种过度增殖之后是阿尔辛蓝阳性细胞外基质的产生和积累,该基质抵抗透明质酸酶的消化。在6周时可见细胞活跃的软骨。第一组接受额骨和顶骨平坦部分下方硬脑膜的动物未出现软骨生成。电子显微镜显示,缝合处硬脑膜内层存在蛋白聚糖样基质和II型胶原,鳞状硬脑膜和缝合处硬脑膜外层以致密的I型胶原为主。本实验的重要发现是:(1)异位移植的新生硬脑膜可诱导成骨;(2)硬脑膜的这种异位骨诱导需要上皮间充质相互作用;(3)将硬脑膜分为缝合处硬脑膜和鳞状硬脑膜,前者除成骨外偶尔还会发生软骨生成,而后者仅发生膜内成骨,表明硬脑膜内存在内在差异。这种硬脑膜异质性得到了直接超微结构数据的支持。