Department of Oral and Maxillofacial Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany.
Histochem Cell Biol. 2020 Oct;154(4):397-403. doi: 10.1007/s00418-020-01904-7. Epub 2020 Jul 24.
Dental follicle cells (DFCs) are progenitor cells for mineralizing cells such as alveolar osteoblasts, but little is known about the mechanisms of the differentiation. Interestingly, different cell lines sometimes have different potentials to differentiate into mineralizing cells. In this study, we compared two different DFC lines, with one cell line (DFC_B) showing a high alkaline phosphatase (ALP) activity in long-term cultures with standard medium and a reliable mineralizing potential. However, the other cell line DFC_A shows low ALP activity in standard medium and almost no mineralization. Known osteogenic markers such as RUNX2 were similarly expressed in both cell lines. However, the proosteogenic signaling pathway of the bone morphogenetic protein (BMP) is induced in DFC_B, and the parathyroid hormone-related protein (PTHrP), which is involved in tooth root development, was also expressed more strongly. Previous studies have shown that the secreted PTHrP negatively regulate the transition from pre-osteoblastic progenitors to osteoblasts, but we showed that an inhibition of PTHrP gene expression reduced the ALP activity and the BMP-signaling pathway. In addition, endogenously expressed PTHrP is located in the cell nucleus. In contrast, supplementation of PTHrP or an inhibitor for the PTHrP receptor did not affect the ALP activity of DFC_B. In conclusion, our data suggest that a high endogenous expression of PTHrP in DFCs supports the induction of osteogenic differentiation via an intracrine mode.
牙滤泡细胞（DFC）是矿化细胞（如牙槽骨细胞）的祖细胞，但对于其分化的机制知之甚少。有趣的是，不同的细胞系有时具有不同的分化为矿化细胞的潜力。在这项研究中，我们比较了两种不同的 DFC 系，其中一种细胞系（DFC_B）在标准培养基中长期培养时具有较高的碱性磷酸酶（ALP）活性和可靠的矿化潜能。然而，另一种细胞系 DFC_A 在标准培养基中显示出较低的 ALP 活性，几乎没有矿化。两种细胞系中均表达了已知的成骨标志物，如 RUNX2。然而，骨形态发生蛋白（BMP）的前成骨信号通路在 DFC_B 中被诱导，而参与牙根发育的甲状旁腺激素相关蛋白（PTHrP）也表达得更强。先前的研究表明，分泌的 PTHrP 负调控前成骨细胞向成骨细胞的转化，但我们发现抑制 PTHrP 基因表达会降低 ALP 活性和 BMP 信号通路。此外，内源性表达的 PTHrP 位于细胞核中。相比之下，补充 PTHrP 或 PTHrP 受体抑制剂不会影响 DFC_B 的 ALP 活性。总之，我们的数据表明，DFC 中高内源性表达的 PTHrP 通过胞内模式支持成骨分化的诱导。
