Effects of Sodium Fluoride Treatment In Vitro on Cell Proliferation, BMP-2 and BMP-3 Expression in Human Osteosarcoma MG-63 Cells

摘要

Chronic excessive fluoride intake may cause fluorosis, which chiefly manifests as bone damage (or skeletal fluorosis). However, the molecular mechanism of skeletal fluorosis has not been clarified up to the present. The objective of this study was to analyze the effects of fluoride treatment on two of bone morphogenetic protein family member (BMP-2 and BMP-3) expression and cell viability using human osteosarcoma MG-63 cells as a model. Sodium fluoride (NaF) had pro-proliferation effects at relatively moderate concentration, with 5 x 10(3) mu mol/L having the best effects. At 2 x 10(4) mu mol/L, NaF inhibits cell proliferation. BMP-2 and BMP-3 expression was significantly induced by 5 x 10(3) mu mol/L NaF and, to lesser extent, by 2 x 10(4) mu mol/L NaF. Correspondingly, mothers against decapentaplegic homolog 1 (Smad-1) increased at both doses of NaF, which indicated the BMP signaling pathway was activated. Notable increases in secreted alkaline phosphatase (ALP) were observed when cells were treated with 5 x 10(3) mu mol/L NaF. A BMP specific inhibitor LDN193189 suppressed cell proliferation induced by 5 x 10(3) mu mol/L NaF. Also, 2 x 10(4) mu mol/L NaF induced apoptosis but likely through a mechanism unrelated to the BMP pathway. Collectively, data show that NaF had dose-dependent effects on cell proliferation as well as BMP-2 and BMP-3 expression in MG-63 cells and suggested that cell proliferation enhanced by NaF-induced BMP members may be a molecular mechanism underlying skeletal fluorosis.