FLUOROALUMINATE INDUCES PERTUSSIS-TOXIN-SENSITIVE PROTEIN-PHOSPHORYLATION - DIFFERENCES IN MC3T3-E1 OSTEOBLASTIC AND NIH3T3 FIBROBLASTIC CELLS

Fluoride is an acknowledged bone-forming agent that may act through st imulation of osteoblast proliferation. Fluoride's action on osteoblast s and bone is potentiated by aluminum, which can form a complex with f luoride (fluoroaluminate) and activate heterotrimeric G proteins. Here we examined signaling pathways activated by fluoroaluminate in MC3T3- E1 osteoblastic and in NIH3T3 fibroblastic cells. In MC3T3-E1 cells, f luoroaluminate induced a decrease in cAMP levels and an increase in MA P and p70 S6 kinase phosphorylatians. These responses were partially o r completely prevented by pertussis toxin, an inhibitor of G alpha i p roteins. In NIH3T3 cells, fluoroaluminate induced weaker tyrosine and MAP kinase phosphorylations. Fluoroaluminate, but not PDGF, induced a long-lasting tyrosine phosphorylation of a 130 kDa protein only in MC3 T3-E1 cells. The expression of G alpha i2, but not of G alpha s and G alpha q/11 proteins was about 10-fold higher in MC3T3-E1 cells. Thus, different signaling in osteoblastic and fibroblastic cells may be due to differential expression of G alpha i proteins and tyrosine kinase s ubstrates and could underlie fluoride's pharmacological action in bone . (C) 1997 Academic Press.