The Advanced Oral Health Science Research Center, Iwate Medical University, Iwate, Japan.
J Cell Physiol. 2011 Oct;226(10):2527-34. doi: 10.1002/jcp.22597.
During tooth development, inner enamel epithelial (IEE) cells differentiate into enamel-secreting ameloblasts, a polarized and elongated cellular population. The molecular underpinnings of this morphogenesis and cytodifferentiation, however, are not well understood. Here, we show that Rho-associated coiled-coil-containing protein kinase (ROCK) regulates ameloblast differentiation and enamel formation. In mouse incisor organ cultures, inhibition of ROCK, hindered IEE cell elongation and disrupted polarization of differentiated ameloblasts. Expression of enamel matrix proteins, such as amelogenin and ameloblastin, and formation of the terminal band structure of actin and E-cadherin were also perturbed. Cultures of dental epithelial cells revealed that ROCK regulates cell morphology and cell adhesion through localization of actin bundles, E-cadherin, and β-catenin to cell membranes. Moreover, inhibition of ROCK promoted cell proliferation. Small interfering RNA specific for ROCK1 and ROCK2 demonstrated that the ROCK isoforms performed complementary functions in the regulation of actin organization and E-cadherin-mediated cell-cell adhesion. Thus, our results have uncovered a novel role for ROCK in amelogenesis.
在牙齿发育过程中，内釉上皮（IEE）细胞分化为分泌釉质的成釉细胞，这是一种极化和伸长的细胞群体。然而，这种形态发生和细胞分化的分子基础尚不清楚。在这里，我们表明 Rho 相关卷曲螺旋蛋白激酶（ROCK）调节成釉细胞分化和釉质形成。在小鼠切牙器官培养物中，抑制 ROCK 会阻碍 IEE 细胞的伸长并破坏分化的成釉细胞的极化。釉基质蛋白的表达，如釉原蛋白和釉蛋白，以及肌动蛋白和 E-钙黏蛋白的终带结构的形成也受到干扰。牙上皮细胞的培养表明，ROCK 通过将肌动蛋白束、E-钙黏蛋白和β-连环蛋白定位到细胞膜上来调节细胞形态和细胞黏附。此外，抑制 ROCK 可促进细胞增殖。针对 ROCK1 和 ROCK2 的小干扰 RNA 表明，ROCK 同工型在调节肌动蛋白组织和 E-钙黏蛋白介导的细胞间黏附中发挥互补作用。因此，我们的研究结果揭示了 ROCK 在釉质发生中的新作用。
