Deletion of epithelial cell-specific p130Cas impairs the maturation stage of amelogenesis

Deletion of epithelial cell-specific p130Cas impairs the maturation stage of amelogenesis
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DOI:
10.1016/j.bone.2021.116210
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发表时间:
2021-10-11
期刊:
影响因子:
4.1
通讯作者:
Jimi, Eijiro
Jimi, Eijiro
中科院分区:
医学2区
文献类型:
--
作者:
Inoue, Akane;Kiyoshima, Tamotsu;Jimi, Eijiro

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成釉细胞的形成分为分泌期、过渡期、成熟期和后成熟期,各期成釉细胞的形态变化与其功能密切相关。p130 Crk相关底物(Cas)是一种调节细胞粘附、细胞骨架变化和极化等重要细胞过程的支架蛋白。p130 Cas在成釉细胞从分泌期到成熟期均有表达。上皮细胞特异性p130 Cas缺陷(p130 Cas(Delta epi-))小鼠表现出釉质矿化不足,年轻小鼠的下颌切牙呈白垩样白色,老年小鼠磨牙磨损。显微计算机断层扫描分析和维氏显微硬度测试显示,与p130 Cas(flox/flox)小鼠相比,p130 Cas(Delta epi-)小鼠的釉质更薄,釉质矿物质密度和硬度更低。扫描电子显微镜和能量色散X射线光谱分析表明,釉杆结构的干扰和较低的Ca和P含量在p130 Cas(Δ epi-)小鼠,分别。在p130 Cas(Delta epi-)小鼠中观察到成釉细胞排列紊乱,尤其是在成熟期。此外,釉基质蛋白的表达水平,如釉原蛋白和成釉蛋白在分泌阶段,和功能标志物,如碱性磷酸酶和铁的积累,和Na+/Ca 2 ++K+-交换在成熟阶段在p130 Cas(Δ epi-)小鼠降低。提示p130 Cas在釉质形成中起重要作用。
Amelogenesis consists of secretory, transition, maturation, and post-maturation stages, and the morphological changes of ameloblasts at each stage are closely related to their function. p130 Crk-associated substrate (Cas) is a scaffold protein that modulates essential cellular processes, including cell adhesion, cytoskeletal changes, and polarization. The expression of p130Cas was observed from the secretory stage to the maturation stage in ameloblasts. Epithelial cell-specific p130Cas-deficient (p130Cas(Delta epi-)) mice exhibited enamel hypomineralization with chalk-like white mandibular incisors in young mice and attrition in aged mouse molars. A micro-computed tomography analysis and Vickers micro-hardness testing showed thinner enamel, lower enamel mineral density and hardness in p130Cas(Delta epi-) mice in comparison to p130Cas(flox/flox) mice. Scanning electron microscopy, and an energy dispersive X-ray spectroscopy analysis indicated the disturbance of the enamel rod structure and lower Ca and P contents in p130Cas(Delta epi-) mice, respectively. The disorganized arrangement of ameloblasts, especially in the maturation stage, was observed in p130Cas(Delta epi-)mice. Furthermore, expression levels of enamel matrix proteins, such as amelogenin and ameloblastin in the secretory stage, and functional markers, such as alkaline phosphatase and iron accumulation, and Na+/Ca2++K+-exchanger in the maturation stage were reduced in p130Cas(Delta epi-)mice. These findings suggest that p130Cas plays important roles in amelogenesis (197 words).