Influence of Low Level Sodium Fluoride on Expression of IGF-1 and IGF-2 Protein in Experimental Type 2 Diabetes with Periodontitis Model

Abstract

Dysregulation of growth and inflammatory mediators might contribute to defective tissue homeostasis and healing, as commonly observed in sedentary lifestyles and in conditions such as diabetes mellitus and periodontitis. Periodontitis is an inflammatory disease characterized by extensive bone resorption. Sodium fluoride (NaF) causes proliferation and differentiation, and modulates the activity of growth factors. In this study, we investigated the effects of NaF on insulin-like growth factor (IGF) 1 and 2 in Goto-Kakizaki (GK) rats, a spontaneous model of type 2 diabetes induced by Porphyromonas gingivalis, an important colonizer of the oral cavity that has been implicated in periodontitis. NaF strongly inhibited the P. gingivalis-induced alveolar bone loss. That effect was accompanied by decreased levels of TNF-IL-1 , and RM4, which were upregulated in P. gingivalis-induced diabetes model. Consistent with the anti-inflammatory effect, NaF inhibited osteoclast markers, the receptor activator of nuclear factor kappa B ligand (RANKL) and Cathepsin K protein expression. IGF-1, -2 was strongly expressed by periodontal ligament, fibroblasts, particularly those in areas close to cementum and bone surfaces in NaF-treated groups. In the periodontal ligament, strong staining was noted in the fiber bundles inserting into alveolar bone and cementum. Our findings suggest the mechanism of IGF signaling by which NaF alters periodontal tissue repair in type 2 diabetes.

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

“…A recent study confirmed that the expression of IGF-1, IFG-2, IFG-1R, and IGF-2R increased after NaF treatment, while the expression of TNF-α, IL-1β, RANKL, and cathepsin K decreased. These effects contributed to attenuated alveolar bone resorption caused by a low concentration of NaF [94].…”

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.…”