Objective To examine the combined effects of sodium fluoride and sodium arsenite on the Runx2 signaling pathway of bone metabolism in rats.
Methods Factorial experimental design was used. SD rats were exposed to NaF (5mg/kg and 20 mg/kg), NaAsO2 (2.5 mg/kg and 10 mg/kg), and 4 combinations of NaF plus NaAsO2 by oral perfusion for 6 months respectively. The concentrations of urinary fluoride (UF) and urinary arsenic (UAs) were determined as exposure biomarkers by fluoride ion selective electrode method and inductively coupled plasma optical emission spectrometer, respectively. The concentrations of parathyroid hormone (PTH), protein kinase A (PKA), cAMP-response element binding protein (CREB), and runt-related transcription factor 2 (Runx2) in serum were determined as effect biomarkers by enzyme-linked immunosorbent assay (ELISA).
Results A positive correlation was identified between the concentrations of UF & UAs and the exposure dose of fluoride & arsenite (P<0.01). The fluoride was positively associated with the Runx2, PTH, PKA, and CREB (r=0.626, 0.489, 0.534, 0.363, respectively, P<0.05 or P<0.01). The arsenite was positively associated with the PTH, and PKA (r=0.336, 0.374, respectively, P<0.05 or P<0.01), but negatively correlated with the Runx2 (r=-0.376, P<0.05). There was an interaction between F & As and Runx2 (F=3.928, P<0.01). Runx2 level was lower in the rats treated with 20mg/kg F+2.5mg/kg As or 20mg/kg F+10mg/kg As than that in those treated with F or As separately.
Conclusion The PTH-PKA-CREB-Runx2 pathway participates in the fluoride induced bone damage, while arsenite indirectly participates in this process by affecting Runx2. The combined effects of F and As on Runx2 are an antagonism effect of NaF (20 mg/kg) plus NaAsO2 (2.5 mg/kg) and NaF (20 mg/kg) plus NaAsO2 (10 mg/kg).
DownLoad: