Department of Periodontology and Endodontology, Tohoku University Graduate School of Dentistry, Sendai, Japan.
Department of Oral Diagnosis, Tohoku University Graduate School of Dentistry, Sendai, Japan.
J Periodontal Res. 2016 Apr;51(2):164-74. doi: 10.1111/jre.12294. Epub 2015 Jun 12.
BACKGROUND AND OBJECTIVE: Dental follicle cells, putative progenitor cells for cementoblasts, osteoblasts and periodontal ligament cells, interplay with Hertwig's epithelial root sheath (HERS) cells during tooth root formation, in which HERS is considered to have an inductive role in initiating cementogenesis by epithelial-mesenchymal interaction. However, the specific mechanisms controlling the cementoblast/osteoblast differentiation of dental follicle cells are not fully understood. Canonical Wnt signaling has been implicated in increased bone formation by controlling mesenchymal stem cell or osteoblastic cell functions. This study examined the possible expression of canonical Wnt ligand in HERS and the role of Wnt signaling during the cementoblast/osteoblast differentiation of dental follicle cells. MATERIAL AND METHODS: The expression of Wnt3a, a representative canonical Wnt ligand, in HERS was assessed by immunohistochemistry. The differentiation and function of immortalized murine dental follicle cells were evaluated by measuring alkaline phosphatase (ALP, Alpl) activity and osteogenic gene expression. RESULTS: We identified the expression of Wnt3a in HERS during mouse tooth root development by immunohistochemistry as well as in cultured human epithelial rest cells of Malassez by real-time polymerase chain reaction, while no expression of Wnt3a was detected in cultured dental mesenchymal cells. Exposure of immortalized murine dental follicle cells to Wnt3a-induced ALP activity as well as expression of the Alpl gene. Pretreatment of cells with Dickkopf-1, a potent canonical Wnt antagonist, markedly attenuated the effect of Wnt3a on ALP expression. Furthermore, Wnt3a induced transcriptional activity of runt-related transcription factor 2 (Runx2) and expression of osterix at gene and/or protein levels. Treatment with osterix-small interfering RNA significantly inhibited Wnt3a-induced ALP expression at gene and protein levels. CONCLUSION: These findings suggest that HERS has a potential role in stimulating cementoblast/osteoblast differentiation of dental follicle cells via the Wnt/β-catenin signaling pathway.
背景与目的：牙囊细胞是成牙骨质细胞、成骨细胞和牙周膜细胞的祖细胞，在牙根形成过程中与 Hertwig 上皮根鞘（HERS）细胞相互作用，HERS 被认为通过上皮-间充质相互作用在启动牙骨质发生中具有诱导作用。然而，控制牙囊细胞成牙骨质细胞/成骨细胞分化的具体机制尚不完全清楚。经典 Wnt 信号通路通过控制间充质干细胞或成骨细胞的功能参与增加骨形成。本研究检测了 HERS 中经典 Wnt 配体的可能表达，并研究了 Wnt 信号通路在牙囊细胞成牙骨质细胞/成骨细胞分化中的作用。
材料与方法：通过免疫组织化学检测 HERS 中经典 Wnt 配体 Wnt3a 的表达。通过测量碱性磷酸酶（ALP，Alpl）活性和骨形成基因表达来评估永生化鼠牙囊细胞的分化和功能。
结果：我们通过免疫组织化学检测到 Wnt3a 在小鼠牙根发育过程中的表达，以及在培养的人 Malassez 上皮根鞘细胞中的表达，而在培养的牙间质细胞中未检测到 Wnt3a 的表达。Wnt3a 诱导永生化鼠牙囊细胞的 ALP 活性和 Alpl 基因的表达。细胞用 Dickkopf-1（一种有效的经典 Wnt 拮抗剂）预处理，可显著减弱 Wnt3a 对 ALP 表达的影响。此外，Wnt3a 诱导 runt 相关转录因子 2（Runx2）和骨基质 Gla 蛋白（osterix）基因和/或蛋白水平的转录活性。用 osterix-siRNA 处理可显著抑制 Wnt3a 诱导的 ALP 基因和蛋白表达。
结论：这些发现表明，HERS 通过 Wnt/β-catenin 信号通路在刺激牙囊细胞成牙骨质细胞/成骨细胞分化中具有潜在作用。
Exp Cell Res. 2015-8-1
J Periodontal Res. 2011-12-11
Biochem Biophys Res Commun. 2016-9-16
Connect Tissue Res. 2012-3-21
Int J Oral Sci. 2023-11-24
Int J Mol Sci. 2023-10-26
Pharmaceuticals (Basel). 2023-7-19
Zotero 插件