Micromolar Levels of Sodium Fluoride Promote Osteoblast Differentiation Through Runx2 Signaling

Abstract

Bone remodeling is a vital physiological process of healthy bone tissue in humans. Imbalances in this vital process lead to pathological conditions, including periodontal diseases. In this study, we characterized the effects of micromolar levels of NaF on the proliferation and osteogenic differentiation of MC3T3-E1 osteoblastic cells. NaF significantly enhanced the proliferation, alkaline phosphatase (ALP) activity, and mineralization of MC3T3-E1 cells. Quantitative real-time PCR analysis revealed that the expression of mRNAs encoding runt-related transcription factor 2 (Runx2), Osterix, Osteopontin and Osteocalcin was up-regulated in NaF-treated MC3T3-E1 cells compared with untreated controls. Western blot analysis demonstrated that Runx2 and Osterix were inhibited by Runx2 siRNA but were re-activated by treatment with NaF. Furthermore, in vivo evidence indicated that NaF protects against Porphyromonas gingivalis-induced periodontal inflammation and alveolar bone loss in a P. gingivalis-challenged experimental periodontitis animal model. These data suggest that NaF promotes the osteoblastic differentiation of MC3T3-E1 cells through the Runx2/Osterix pathway and may be effective for the treatment of bone-related disorders.

Evaluation of the bioactivity of fluoride‐enriched mineral trioxide aggregate on osteoblasts

“…Fluoride improved the MTA-altered cell behaviour by proliferation enhancement and differentiation boosting of alveolar osteoblasts, thereby confirming current knowledge on the action of sodium fluoride on bone cells (Everett 2011, Lee et al 2017. Of note, the effects seen in the present study originate from fluoride that was eluted from MTA discs, which means that fluoride-enriched MTA does release bioactive fluoride.…”

“…However, little attention has been paid so far to the biocompatibility testing of MTA supplied with additives (Karygianni et al 2016), which furthermore have not been selected according to their cell-or tissue-supporting capabilities. All of these requests are met by fluoride (Everett 2011, Lee et al 2017, thus rendering it an attractive candidate for the development of a new MTA cement (Gandolfi & Prati 2010, Gandolfi et al 2011. All of these requests are met by fluoride (Everett 2011, Lee et al 2017, thus rendering it an attractive candidate for the development of a new MTA cement (Gandolfi & Prati 2010, Gandolfi et al 2011.…”

“…Such additives would ideally (i) foster bone and/or pulp cell proliferation and differentiation, and hence increase hard tissue formation, whilst simultaneously (ii) being nontoxic and legally approved as a drug, and (iii) exerting antimicrobial actions. All of these requests are met by fluoride (Everett 2011, Lee et al 2017, thus rendering it an attractive candidate for the development of a new MTA cement (Gandolfi & Prati 2010, Gandolfi et al 2011. Fluoride is reported to enhance bone mass and increase the stability of calcified tissues in vivo, whilst encouraging proliferation and osteogenic differentiation in a dose-dependent manner at the cellular level (Everett 2011).…”

Treatment with low‐level sodium fluoride on wound healing and the osteogenic differentiation of bone marrow mesenchymal stem cells

“…In recent years, great advances have been made in elucidating the effects of treating cells with sodium fluoride (NaF) . Those effects have been found to be concentration‐dependent with micromolar levels (low level) of fluoride increasing cell proliferation, while millimolar levels (high concentration) induce stress in the endoplasmic reticulum, apoptosis, and DNA fragmentation by the caspase‐mediated pathway in enamel organ/epithelial‐derived cell lines .…”

“…There have been studies that evaluated the efficacy of low‐level NaF to stimulate epithelial cells and osteoblasts. However, the associated molecular regulatory network is not well understood . Additionally, the role of NaF in the homing of BMMSCs has not been explored to date.…”