Department of Oral Health Sciences, Faculty of Nursing and Welfare, Kyushu University of Nursing and Social Welfare, 888 Tominoo, Tamana, Kumamoto, 865-0062, Japan.
Division of Oral Science for Health Promotion, Department of Oral Health and Welfare, Niigata University Graduate School of Medical and Dental Sciences, 2-5274 Gakkocho-dori, Chuo-ku, Niigata, 951-8514, Japan.
Cell Tissue Res. 2017 Sep;369(3):497-512. doi: 10.1007/s00441-017-2632-x. Epub 2017 May 26.
The mechanisms regulating the maintenance of quiescent adult stem cells in teeth remain to be fully elucidated. Our aim is to clarify the relationship between BrdU label-retaining cells (LRCs) and sonic hedgehog (Shh) signaling in murine teeth. After prenatal BrdU labeling, mouse pups were analyzed during postnatal day 1 (P1) to week 5 (P5W). Paraffin sections were processed for immunohistochemistry for BrdU, Sox2, Gli1, Shh, Patched1 (Ptch1) and Ki67 and for in situ hybridization for Shh and Ptch1. Dense LRCs, Gli1-(+) cells and Ptch1-(+) cells were co-localized in the outer enamel epithelium of the apical bud and apical dental papilla of incisors. In developing molars, dense LRCs were numerous at P1 but then decreased in number over the course of odontogenesis and were maintained in the center of pulp tissue. Gli1-(+) cells were maintained in the pulp horn during the examined stages, while they increased in number and were maintained in the center of pulp tissue during P2-5W. Ptch1-(+) cells were localized in the pulp horn at P1 and increased in number in the center of the pulp after P3W. Shh mRNA was first expressed in the enamel epithelium and then shifted to odontoblasts and other pulp cells. Shh protein was distributed in the epithelial and mesenchymal tissues of incisors and molars. These findings suggest that quiescent dental stem cells are regulated by Shh signaling, and that Shh signaling plays a crucial role in the differentiation and integrity of odontoblasts during epithelial-mesenchymal interactions and dentinogenesis.
调节牙齿静止性成体干细胞维持的机制仍有待充分阐明。我们的目的是阐明鼠牙中 BrdU 标记保留细胞（LRC）与 sonic hedgehog（Shh）信号之间的关系。在产前 BrdU 标记后，在出生后第 1 天（P1）至第 5 周（P5W）分析小鼠幼仔。对石蜡切片进行 BrdU、Sox2、Gli1、Shh、Patched1（Ptch1）和 Ki67 的免疫组织化学以及 Shh 和 Ptch1 的原位杂交处理。在切牙的根尖芽和根尖牙乳头的外釉上皮中，密集的 LRC、Gli1(+)细胞和 Ptch1(+)细胞共定位。在发育中的磨牙中，在 P1 时存在大量密集的 LRC，但在牙发生过程中数量减少，并在牙髓组织的中心保持不变。Gli1(+)细胞在检查阶段保持在牙髓角，而在 P2-5W 期间其数量增加并保持在牙髓组织的中心。Ptch1(+)细胞在 P1 时位于牙髓角，在 P3W 后在牙髓中心数量增加。Shh mRNA 首先在釉质上皮中表达，然后转移到成牙本质细胞和其他牙髓细胞中。Shh 蛋白分布在切牙和磨牙的上皮和间充质组织中。这些发现表明静止性牙源性干细胞受 Shh 信号调节，Shh 信号在釉质上皮-间充质相互作用和牙本质发生过程中成牙本质细胞的分化和完整性中发挥关键作用。
