Type XVII Collagen is a Key Player in Tooth Enamel Formation
Type XVII Collagen is a Key Player in Tooth Enamel Formation
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DOI：
10.2353/ajpath.2009.080573
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发表时间：
2009-01-01
影响因子：
6
通讯作者：
Shimizu, Hiroshi
中科院分区：
文献类型：
--
作者：
Asaka, Takuya;Akiyama, Masashi;Shimizu, Hiroshi
遗传性牙釉质发育不全是由于编码主要牙釉质成分的基因突变而发生的。釉质发育不全也曾在交界性大疱性表皮中报道过，这是由编码XVII型胶原（COL 17）的基因突变引起的，XVII型胶原是上皮-间充质交界处的一种成分。为了阐明上皮-间充质连接分子（如COL 17）缺乏引起的釉质发育不全的病理机制，我们研究了我们最近建立的Col 17（-/-）和Col 17拯救小鼠的牙齿形成。与野生型小鼠相比，Col 17（-/-）小鼠的门牙表现出减少黄色色素沉着，减少铁沉积，延迟钙化，和显着不规则的釉质棱柱，表明存在釉质发育不全。Col 17（-/-）小鼠的磨牙表现出严重的咬合磨损。这些异常在Col 17拯救的人源化小鼠中得到纠正。因此，Col 17（-/-）小鼠清楚地再现了人类交界性大疱性表皮松质病患者的釉质发育不全。我们能够研究Col 17（-/-）小鼠的牙齿形成，因为Col 17（-/-）基因型不是致命的。Col 17（-/-）小鼠切牙的成釉细胞分化较差，缺乏分泌釉质蛋白的Tomes突起，釉原蛋白、成釉蛋白和其他釉质基因的mRNA表达降低。这些发现表明，COL 17调节成釉细胞分化，是Tomes'过程的正常形成所必需的。总之，COL 17缺陷破坏了上皮-间充质相互作用，导致成釉细胞分化缺陷和釉质畸形。(Am J Pathol 2009，174：91-100; DOI 10.2353/ajpath.2009.080573）
Inherited tooth enamel hypoplasia occurs due to mutations in genes that encode major enamel components. Enamel hypoplasia also has been reported in junctional epidermolysis bullosa, caused by mutations in the genes that encode type XVII collagen (COL17), a component of the epithelial-mesenchymal junction. To elucidate the pathological mechanisms of the enamel hypoplasia that arise from the deficiency of epithelial-mesenchymal junction molecules, such as COL17, we investigated tooth formation in our recently established Col17(-/-) and Col17 rescued mice. Compared with wild-type mice, the incisors of the Col17(-/-) mice exhibited reduced yellow pigmentation, diminished iron deposition, delayed calcification, and markedly irregular enamel prisms, indicating the presence of enamel hypoplasia. The molars of the Col17(-/-) mice demonstrated advanced occlusal wear. These abnormalities were corrected in the Col17 rescued humanized mice. Thus, the Col17(-/-) mice clearly reproduced the enamel hypoplasia in human patients with junctional epidermolysis bullosa. We were able to investigate tooth formation in the Col17(-/-) mice because the Col17(-/-) genotype is not lethal. Col17(-/-) mouse incisors had poorly differentiated ameloblasts that lacked enamel protein-secreting Tomes' processes and reduced mRNA expression of amelogenin, ameloblastin, and of other enamel genes. These findings indicated that COL17 regulates ameloblast differentiation and is essential for normal formation of Tomes' processes. in conclusion, COL17 deficiency disrupts the epithelial-mesenchymal interactions, leading to both defective ameloblast differentiation and enamel malformation. (Am J Pathol 2009, 174:91-100; DOI 10.2353/ajpath.2009.080573)