Sodium fluoride regulates the osteo/odontogenic differentiation of stem cells from apical papilla by modulating autophagy

Abstract

Fluoride (sodium fluoride) is thought to be essential in the development of tooth, and research shows that fluoride can modulate the differentiation of dental stem cells. However, the effects of fluoride on the committed differentiation of stem cells from apical papilla (SCAPs) and the underlying mechanisms remain unclear. Here, SCAPs were isolated from healthy extracted human third molars with immature roots and then were cultured with NaF conditioned media. Cell Counting Kit‐8, EdU staining, and flow cytometry were performed to detected the proliferation activity. Alkaline phosphatase (ALP) activity, Alizarin Red staining, Western blot assay, and real‐time reverse‐transcription polymerase chain reaction were applied to assess the osteo/odontogenic differentiation NaF‐treated SCAPs. Western blot assay and transmission electron microscope were used to evaluate the autophagy involved in the differentiation of SCAPs. ALP activity, ALP protein, and messenger RNA (mRNA) expression showed that 0.5 mM was the optimal concentration for the induction of SCAPs by NaF. 0.5 mM NaF‐treated SCAPs induced more mineralized nodules as compared with untreated cells. Moreover, the osteo/odontogenic markers (RUNX2, OSX, DSP, and OCN) in mRNA levels were upregulated while the protein levels of these markers increased considerably in 0.5 mM NaF‐treated SCAPs. Furthermore, the autophagy‐related proteins (LC3, ATG5, and Beclin1) increased in NaF‐treated SCAPs, and the osteo/odontogenic makers significantly decreased while silencing ATG5 to block autophagy. In all, sodium fluoride can regulate the osteo/odontogenic differentiation of SCAPs by modulating autophagy.

iRoot BP Plus promotes osteo/odontogenic differentiation of bone marrow mesenchymal stem cells via MAPK pathways and autophagy

“…Alkaline phosphatase (ALP) has a vital function during the formation of hydroxyapatite crystal, which is the initial phase in mineralization of osteoblasts and odontoblasts [26], and its activity is upregulated at an early stage of calcification [36]. Therefore, many studies used ALP as an early-stage marker of osteo/odontoblastic differentiation [25, 37]. In the present study, 0.2 mg/ml was the optimal concentration of BP-CM to promote differentiation of BMMSCs through detecting the ALP activity at days 3, 5, and 7, as well as the gene level of Alp at day 5.…”

“…TEM was performed to observe autophagosomes as described previously [25]. BMMSCs were harvested and fixed with 2.5% glutaraldehyde.…”

Upregulation of Parkin Accelerates Osteoblastic Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells and Bone Regeneration by Enhancing Autophagy and β-Catenin Signaling

“…Accumulating evidence indicates that autophagy plays a crucial role in the regulation of bone homeostasis (Nollet et al, 2014;Gomez-Puerto et al, 2016). Autophagy enhances osteoblastic differentiation of BMSCs (Wan et al, 2017;Pan et al, 2019). Autophagy also regulates mesenchymal stem cell properties and senescence during bone aging (Ma et al, 2018).…”

Extracellular IL-37 Enhances Osteogenic and Odontogenic Differentiation of Human Dental Pulp Stem Cells via Autophagy Pathway

“…Autophagy is also an essential process that maintains mineralizing capacity, and balance the population of osteoblasts and osteoclasts [31]. The members in our team have demonstrated that autophagy is involved in the odontogenic and osteogenic differentiation in stem cells of apical papilla and rBMMSCs [32,33].…”