Abstract
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.
Highlights
Dental stem cells such as dental follicle cells (DFCs) could be used in the future to cure oral diseases (Morsczeck and Reichert 2018; Zhang et al 2019a; Zhou et al 2019) and were already successfully used for the regeneration of craniofacial bone in numerous animal studies and case reports in humans (Sybil et al 2020)
parathyroid hormone-related protein (PTHrP) is expressed in the tooth germ and a recent article describes that a great amount of PTHrPexpressing Dental follicle cells (DFCs) become tooth root cells such as periodontal ligament cells, alveolar osteoblasts and cementoblasts (Nagata et al 2020; Takahashi et al 2019)
The alkaline phosphatase (ALP) activity could not be induced with dexamethasone, a strong mineralization was achieved after 4 weeks in dexamethasone-based osteogenic differentiation medium
Summary
Dental stem cells such as dental follicle cells (DFCs) could be used in the future to cure oral diseases (Morsczeck and Reichert 2018; Zhang et al 2019a; Zhou et al 2019) and were already successfully used for the regeneration of craniofacial bone in numerous animal studies and case reports in humans (Sybil et al 2020). The PPR is described as a link between stem/progenitor cells and the vascular niche in the bone microenvironment
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