Biphasic Functions of Sodium Fluoride (NaF) in Soft and in Hard Periodontal Tissues

Abstract

Sodium fluoride (NaF) is widely used in clinical dentistry. However, the administration of high or low concentrations of NaF has various functions in different tissues. Understanding the mechanisms of the different effects of NaF will help to optimize its use in clinical applications. Studies of NaF and epithelial cells, osteoblasts, osteoclasts, and periodontal cells have suggested the significant roles of fluoride treatment. In this review, we summarize recent studies on the biphasic functions of NaF that are related to both soft and hard periodontal tissues, multiple diseases, and clinical dentistry.

Keywords: epithelial cells; fluoride; mesenchymal stem cells; miRNA; osteoblasts; osteoclasts; periodontal disease.

Figure 1

A schematic diagram of the biphasic functions of fluoride in osteoblasts. A low concentration of NaF stimulates the expression of fibronectin, vimentin, Runx2, and OSX to promote the expression of osteoblastic genes (OCN and OPN). A high concentration of NaF inhibits Runx2 and induces oxidative stress in osteoblasts.

Figure 2

A schematic diagram of the biphasic functions of fluoride in osteoclasts. A low concentration of NaF inhibits the expression of RANKL, NFATc1, MMP9, and Cathepsin K but induces OPG to bind RANKL. A low concentration of NaF is possibly associated with Blimp1/Bcl6 to repress the expression of osteoclastic genes (MMP9 and Cathepsin K). A high concentration of NaF decreases the expression of OPG while inducing RANKL to bind RANK. Induced NFATc1 translocate into the nucleus to promote osteoclastogenesis.

Figure 3

A schematic diagram of the biphasic functions of fluoride in periodontal disease and epithelium cells. A low concentration of NaF induces fibronectin and laminin-5 to improve wound healing, increases the expression of TWIST1 and FGF2 and its receptor to enhance EMT, and attenuates bone resorption via the induction of IGF-1/2 and their receptors which subsequently suppress RANKL, Cathepsin K, and IL-1β. A high concentration of NaF inhibits extracellular matrix proteinases (MMP-20 and KLK4), and FOXO1 results in fluorosis. A high concentration of NaF induces hypoxia-inducible factor 1-alpha (HIF-1α) and oxidative stress, thus inhibits ATG, Beclin, and LC3-I/II to impair autophagy leading to apoptosis and bone resorption.