Odontoblast death drives cell-rich zone-derived dental tissue regeneration
Odontoblast death drives cell-rich zone-derived dental tissue regeneration
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DOI：
10.1016/j.bone.2021.116010
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发表时间：
2021-06-01
期刊：
影响因子：
4.1
通讯作者：
Mizoguchi, Toshihide
中科院分区：
文献类型：
--
作者：
Zhao, Lijuan;Ito, Shinichirou;Mizoguchi, Toshihide
严重的牙组织损伤诱导成牙细胞死亡，牙髓干细胞和祖细胞（DPSCs）分化为成牙细胞样细胞，有助于修复牙本质。然而，引发这种再生过程的损伤诱导机制仍不清楚。我们的目的是了解无硬组织损伤的成牙细胞死亡对牙再生的影响。在此，我们使用基于Cre/ loxp的策略，证明了定位于巢蛋白gfp阳性和巢蛋白gfp阴性细胞的富细胞区（CZ）细胞在成牙细胞枯竭的情况下增殖并分化为成牙细胞样细胞。再生的成牙细胞样细胞在修复性牙本质形成中起作用。rna测序分析显示，牙髓中成牙髓细胞分化和激活相关基因的表达上调，以响应成牙髓细胞的缺失，即使没有损伤牙组织。在这个再生过程中，I型甲状旁腺激素受体（PTH1R）在成牙本质缺失的牙髓中表达增加，从而促进牙本质的形成。物理损伤牙髓中PTH1R及其下游介质，即磷酸化环AMP反应元件结合蛋白（Ser133）的水平升高。总的来说，成牙细胞死亡触发了PTH1R级联，这可能是诱导cz介导的牙齿再生的治疗靶点。
Severe dental tissue damage induces odontoblast death, after which dental pulp stem and progenitor cells (DPSCs) differentiate into odontoblast-like cells, contributing to reparative dentin. However, the damageinduced mechanism that triggers this regeneration process is still not clear. We aimed to understand the effect of odontoblast death without hard tissue damage on dental regeneration. Herein, using a Cre/LoxP-based strategy, we demonstrated that cell-rich zone (CZ)-localizing Nestin-GFP-positive and Nestin-GFP-negative cells proliferate and differentiate into odontoblast-like cells in response to odontoblast depletion. The regenerated odontoblast-like cells played a role in reparative dentin formation. RNA-sequencing analysis revealed that the expression of odontoblast differentiation- and activation-related genes was upregulated in the pulp in response to odontoblast depletion even without damage to dental tissue. In this regenerative process, the expression of type I parathyroid hormone receptor (PTH1R) increased in the odontoblast-depleted pulp, thereby boosting dentin formation. The levels of PTH1R and its downstream mediator, i.e., phosphorylated cyclic AMP response element-binding protein (Ser133) increased in the physically damaged pulp. Collectively, odontoblast death triggered the PTH1R cascade, which may represent a therapeutic target for inducing CZ-mediated dental regeneration.