Type VII collagen deficiency causesdefective tooth enamel formation due to poor differentiation of ameloblasts
Type VII collagen deficiency causesdefective tooth enamel formation due to poor differentiation of ameloblasts
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由于成釉细胞分化不良，VII 型胶原蛋白缺乏会导致牙釉质形成缺陷
DOI：
10.1016/j.ajpath.2012.07.018
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发表时间：
2012
期刊：
影响因子：
6
通讯作者：
Shimizu H
中科院分区：
文献类型：
--
作者：
Umemoto H;Akiyama M;Domon T;Nomura T;Shinkuma S;Ito K;Asaka T;Sawamura D;Uitto J;Uo M;Kitagawa Y;Shimizu H
隐性营养不良性大疱性表皮病（RDEB）是由编码VII型胶原（COL 7）的基因突变引起的，该基因是表皮基底膜区锚定原纤维的主要成分。RDEB患者的口腔卫生指数低，普遍存在牙齿异常和龋齿。我们研究了牙齿釉质结构的RDEB患者的扫描电子显微镜。它显示不规则的釉质棱柱，表明结构性釉质缺陷。为了阐明由于COL 7缺陷导致的釉质缺陷的病理机制，我们研究了我们建立的Col 7a 1 −/−和COL 7拯救的人源化小鼠的牙齿形成。Col 7a 1 −/−小鼠的牙釉质具有正常的表面结构。Col 7a 1 −/−小鼠的牙釉质钙化和化学成分与野生型相似。然而，Col 7a 1 −/−小鼠牙齿的横切面显示出不规则的釉质棱柱，这也在RDEB患者中观察到。此外，Col 7a 1 −/−小鼠牙齿的成釉细胞分化较差，缺乏正常的釉质蛋白分泌Tomes'过程，并且显示出釉原蛋白和其他釉质相关分子的mRNA表达减少。这些釉质异常在表达人COL 7A 1转基因的COL 7拯救的人源化小鼠中得到纠正。这些发现表明，COL 7调节成釉细胞分化，是必不可少的Tomes'过程的形成。总的来说，COL 7缺陷被认为破坏上皮-间充质相互作用，导致RDEB患者成釉细胞分化缺陷和釉质畸形。
Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in the gene encoding type VII collagen (COL7), a major component of anchoring fibrils in the epidermal basement membrane zone. Patients with RDEB present a low oral hygiene index and prevalent tooth abnormalities with caries. We examined the tooth enamel structure of an RDEB patient by scanning electron microscopy. It showed irregular enamel prisms, indicating structural enamel defects. To elucidate the pathomechanisms of enamel defects due to COL7 deficiency, we investigated tooth formation inCol7a1−/−and COL7-rescued humanized mice that we have established. The enamel fromCol7a1−/−mice had normal surface structure. The enamel calcification and chemical composition ofCol7a1−/−mice were similar to those of the wild type. However, transverse sections of teeth from theCol7a1−/−mice showed irregular enamel prisms, which were also observed in the RDEB patient. Furthermore, theCol7a1−/−mice teeth had poorly differentiated ameloblasts, lacking normal enamel protein–secreting Tomes' processes, and showed reduced mRNA expression of amelogenin and other enamel-related molecules. These enamel abnormalities were corrected in the COL7-rescued humanized mice expressing a humanCOL7A1transgene. These findings suggest that COL7 regulates ameloblast differentiation and is essential for the formation of Tomes' processes. Collectively, COL7 deficiency is thought to disrupt epithelial–mesenchymal interactions, leading to defective ameloblast differentiation and enamel malformation in RDEB patients.