Overexpression of ameloblastin in secretory ameloblasts results in demarcated, hypomineralized opacities in enamel.
Overexpression of ameloblastin in secretory ameloblasts results in demarcated, hypomineralized opacities in enamel.
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DOI：
10.3389/fphys.2023.1233391
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发表时间：
2023
影响因子：
4
通讯作者：
中科院分区：
文献类型：
--
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简介：牙釉质的发育缺陷在牙齿萌出之前就已显现出来，包括釉质发育不全（一种由潜在基因突变引起的罕见疾病）和磨牙-切牙矿化不足（MIH）（一种由环境和表观遗传因素引起的儿童常见疾病）。 MIH 牙釉质表现为异常牙釉质，其特征是半透明性丧失、健康牙釉质和受影响牙釉质之间的分界以及矿物质含量减少。不透明、边界明确的牙釉质病变的病理生理学尚不清楚；然而，有人提出牙釉质蛋白保留在基质中。成釉素 (Ambn) 是一种分泌型钙结合磷蛋白 (SCPP) 的牙釉质蛋白，对牙釉质形成至关重要。当 Ambn 基因突变或缺失时，牙齿就会受到发育不全的釉质生成不全的影响。 方法：在本研究中，当转基因 Ambn 从编码全长 Ambn 的牙釉原启动子过表达时，分析了小鼠牙釉质的形成。在不同的小鼠品系中，Ambn 在六种逐渐增加的浓度下表达不足和过度表达。 结果：过表达 Ambn 的小鼠在低浓度下表现出不透明的牙釉质，在高浓度下表现出界限分明的病变。牙釉质损伤的严重程度从靠近牙本质牙釉质交界处 (DEJ) 的内牙釉质开始增加，跨越划定区域中牙釉质层的整个宽度。与不透明牙釉质相关的是 17-kDa Ambn 裂解产物、延长的分泌阶段和成熟阶段的薄基底膜。在靠近 DEJ 的最里面的牙釉质和矿化前沿发现的 Ambn 积累与矿物质含量的减少相关。界定的牙釉质损伤与 17 kDa 及更高的 Ambn 物种、分泌和过渡阶段延长、基底膜薄以及成熟阶段缩短有关。在周围矿化牙釉质和邻近从牙釉质表面分离的成釉细胞处描绘出矿化不足的混浊。低效的 Ambn 裂解、成釉细胞之间的接触丧失以及基底膜的改变削弱了内吞活性；因此，牙釉质蛋白在基质中保持未吸收。成釉细胞能够通过精细调节的反馈机制区分 Ambn 浓度和 Ambn 裂解产物。小鼠分泌性成釉细胞中 Ambn 的表达不足或过度会导致发育不全的成釉细胞不全或矿化不足，病变边界不透明或界限分明，类似于 MIH。
Introduction: Developmental defects of the enamel manifest before tooth eruption and include amelogenesis imperfecta, a rare disease of underlying gene mutations, and molar–incisor hypomineralization (MIH), a prevalent disease in children originating from environmental and epigenetic factors. MIH enamel presents as the abnormal enamel marked by loss of translucency, demarcation between the healthy and affected enamel, and reduced mineral content. The pathophysiology of opaque, demarcated enamel lesions is not understood; however, the retention of enamel proteins in the matrix has been suggested. Ameloblastin (Ambn) is an enamel protein of the secreted calcium-binding phosphoproteins (SCPPs) critical for enamel formation. When the Ambn gene is mutated or deleted, teeth are affected by hypoplastic amelogenesis imperfecta. Methods: In this study, enamel formation in mice was analyzed when transgenic Ambn was overexpressed from the amelogenin promoter encoding full-length Ambn. Ambn was under- and overexpressed at six increasing concentrations in separate mouse lines. Results: Mice overexpressing Ambn displayed opaque enamel at low concentrations and demarcated lesions at high concentrations. The severity of enamel lesions increased starting from the inner enamel close to the dentino-enamel junction (DEJ) to span the entire width of the enamel layer in demarcated areas. Associated with the opaque enamel were 17-kDa Ambn cleavage products, a prolonged secretory stage, and a thin basement membrane in the maturation stage. Ambn accumulations found in the innermost enamel close to the DEJ and the mineralization front correlated with reduced mineral content. Demarcated enamel lesions were associated with Ambn species of 17 kDa and higher, prolonged secretory and transition stages, a thin basement membrane, and shortened maturation stages. Hypomineralized opacities were delineated against the surrounding mineralized enamel and adjacent to ameloblasts detached from the enamel surface. Inefficient Ambn cleavage, loss of contact between ameloblasts, and the altered basement membrane curtailed the endocytic activity; thus, enamel proteins remained unresorbed in the matrix. Ameloblasts have the ability to distinguish between Ambn concentration and Ambn cleavage products through finely tuned feedback mechanisms. The under- or overexpression of Ambn in murine secretory ameloblasts results in either hypoplastic amelogenesis imperfecta or hypomineralization with opaque or sharply demarcated boundaries of lesions, similar to MIH.
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影响因子：
4
作者：
Pham CD;Smith CE;Hu Y;Hu JC;Simmer JP;Chun YP
通讯作者：
Chun YP
影响因子：
4.2
作者：
Bronckers, A. L. J. J.;Jalali, R.;Lytton, J.
通讯作者：
Lytton, J.
影响因子：
2.7
作者：
Hu, Jan C. -C.;Chun, Yong-Hee P.;Simmer, James P.
通讯作者：
Simmer, James P.
影响因子：
1.3
作者：
Bittencourt, Santos Patricia;Cesario, Fernandes Eloisa
通讯作者：
Cesario, Fernandes Eloisa
影响因子：
9.7
作者：
Houari, Sophia;Derocher, Karen;Babajko, Sylvie
通讯作者：
Babajko, Sylvie