Differential effects of fluoride during the mineralization of osteoblasts from two inbred strains of mice with different bone density

Author(s)

Sandra Satiko Matsuda

• Document type: Doctoral Thesis
• Press: Bauru.
• Institution: Universidade de São Paulo (USP). Faculdade de Odontologia de Bauru (FOB/SDB)
• Defense date: 2010-12-09

Examining board members

Antonio de Castro Rodrigues; Camila Peres Buzalaf; Carla Andreotti Damante; Ana Carolina Magalhães; Juliano Pelim Pessan

• Advisor: Antonio de Castro Rodrigues

Abstract

Fluoride is a natural element found at varying concentrations in drinking water as well as in soil and it is considered a beneficial nutrient at optimal levels. However, although it is well recognized that the fluoride therapy is effective in increasing bone density and it has been used as therapeutic agent to treat osteoporosis, the efficacy in fracture reduction is highly controversial, and exposure to high levels and prolonged time can lead to skeletal fluorosis. The purpose of this study was to investigate the in vitro effects of fluoride exposure during mineralization of two inbread strains, C3H/HeJ (C3) and C57BL/6J (B6), with high and low bone mass respectively. The osteoblasts isolated from newborn mouse calvaria were exposed to several fluoride doses, and the results showed that B6 was more susceptible to NaF, as a reduction in the mineralized area with 10M was already seen; while in C3, the significative dose was with 50 M, indicating that more differentiated osteoprogenitors cells of C3 are more resilient to inhibitory fluoride action. The colony forming unit assays indicate an increase of colony numbers of osteoprogenitors cells and mineralized nodules with NaF treatment. The MMP-2 activity was up-regulated after 7 days of NaF exposure in B6 e down-regulated after 14 and 21 days in C3, showing the distinct coupled action of MMP-2 in different restrictions point during development sequence. The bifasic nature of fluoride responses present by these experimental models indicate that the anabolic action of fluoride is associated to the number of the potential targets (numbers of calvarial osteoprogenitors cells, mesenchymal stem cells), the intrinsic osteoblast activity and the maturation stage of these cells. The cell culture systems can provide molecular and cellular insights, and have the prospective to disclose potential targets and/or better efficacy and safety profile. (AU)