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Stimulation of Sodium‐Dependent Phosphate Transport and Signaling Mechanisms Induced by Basic Fibroblast Growth Factor in MC3T3‐E1 Osteoblast‐like Cells
Author(s) -
Suzuki Atsushi,
Palmer Gaby,
Bonjour JeanPhilippe,
Caverzasio Joseph
Publication year - 2000
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2000.15.1.95
Subject(s) - basic fibroblast growth factor , calphostin c , microbiology and biotechnology , kinase , fibroblast growth factor , calphostin , osteoblast , tyrosine phosphorylation , signal transduction , biology , phosphorylation , paracrine signalling , autocrine signalling , protein kinase c , growth factor , biochemistry , receptor , in vitro
Physiological and pathological observations indicate that basic fibroblast growth factor (bFGF) is an important regulator of osteoblastic cell differentiation and in particular of cranial ossification. Experimental evidence suggests that inorganic phosphate (P i ) transport could be an important function of bone matrix calcification. In the present study, we address the influence of bFGF on P i transport activity in MC3T3‐E1 osteoblast‐like cells derived from mouse calvaria. The results indicate that bFGF is a potent and selective stimulator of sodium‐dependent P i transport in these cells. The change in P i transport activity induced by bFGF depends on transcription and translation and corresponds to a change in the maximum velocity of the P i transport system ( V max ). These observations suggest that enhanced P i transport activity in response to bFGF may result from insertion of newly synthesized P i transporters into the plasma membrane. A selective inhibitor of fibroblast growth factor receptor (FGFR) tyrosine kinase, SU5402, blunted the stimulation of P i transport induced by bFGF. It also prevented the increase in protein tyrosine phosphorylation induced by bFGF, including phosphorylation of FGFR‐1, FGFR‐2, phospholipase C‐γ (PLC‐γ), and Shc as well as the recruitment of the Grb2/Sos signaling complex. In addition, bFGF‐ induced the activation of the mitogen‐activated protein (MAP) kinases extracellular signal–regulated kinase (ERK) and p38, effects that were prevented by SU5402. Both the protein kinase C (PKC) inhibitor calphostin C and PKC down‐regulation suppressed the stimulatory effect of bFGF on P i transport. Selective inhibitors of ERK and p38 MAP kinases slightly reduced this cellular response with a significant effect observed with the highest concentration of the p38 MAP kinase inhibitor. In conclusion, the results of this study indicate that bFGF selectively stimulates P i transport in calvaria‐derived osteoblastic cells. The main signaling mechanism responsible for this effect involves tyrosine phosphorylation of PLC‐γ and activation of PKC, with a possible contribution of the p38 MAP kinase pathway.