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

Background/Aims Lacerations of the oral mucosa and fractures of alveolar processes commonly occur in traumatic dental injuries (TDIs). Impaired wound healing and tissue regeneration have severe consequences on the quality of life. Bone marrow mesenchymal stem cells (BMMSCs) possess the ability of self-renewal and multipotential differentiation. Treatment with low-level sodium fluoride (NaF) has emerged as a promising approach to enhance wound repair. The aim of this study was to assess the effects of low-level NaF on soft tissue healing and on the proliferation, migration and extracellular matrix synthesis of BMMSCs. Material and Methods BMMSCs derived from mice were treated with 50 mu M, 500 mu M, or 5 mM NaF for 12, 24, and 48 hours, and cell proliferation was assessed by the MTS assay. Cell motility was detected at 12 and 24 hours by a wound healing assay, and osteoblastic differentiation for 21 days by 1% Alizarin Red S staining in 50 mu M NaF-treated BMMSCs. Gene expression of Runx2 and Osteocalcin was evaluated by quantitative real-time PCR. An experimental rat skin wound model was employed, and levels of c-Myc, Ki67, fibronectin, and vimentin were assessed by immunohistochemistry. Results There was a significant induction in the proliferation and migration of BMMSCs treated with 50 mu M NaF. The expression of Ki67 and c-Myc protein was increased in tissues treated with 50 mu M NaF, and the expression of fibronectin and vimentin in the 50 mu M NaF-treated tissues was stimulated. Alizarin Red staining revealed enhanced mineralization in 50 mu M NaF-treated BMMSCs with increased expression of Runx2 and Osteocalcin, indicating their upregulated osteogenic differentiation. Conclusion Low-level NaF could promote soft tissue healing and hard tissue regeneration.