Stimulation of sodium-dependent phosphate transport and signaling mechanisms induced by basic fibroblast growth factor in MC3T3-E1 osteoblast- like cells

Atsushi Suzuki, Gaby Palmer, Jean Philippe Bonjour, Joseph Caverzasio

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)95-102
Number of pages8
JournalJournal of Bone and Mineral Research
Volume15
Issue number1
DOIs
Publication statusPublished - 01-01-2000

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Fibroblast Growth Factor 2
Osteoblasts
p38 Mitogen-Activated Protein Kinases
Protein Kinase C
Extracellular Signal-Regulated MAP Kinases
Phosphorylation
Type C Phospholipases
Protein Kinase Inhibitors
Skull
Tyrosine
Receptor, Fibroblast Growth Factor, Type 2
Receptor, Fibroblast Growth Factor, Type 1
sodium phosphate
Fibroblast Growth Factor Receptors
Bone Matrix
Protein C Inhibitor
Mitogen-Activated Protein Kinases
Osteogenesis
Protein-Tyrosine Kinases
Cell Differentiation

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

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title = "Stimulation of sodium-dependent phosphate transport and signaling mechanisms induced by basic fibroblast growth factor in MC3T3-E1 osteoblast- like cells",
abstract = "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.",
author = "Atsushi Suzuki and Gaby Palmer and Bonjour, {Jean Philippe} and Joseph Caverzasio",
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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. / Suzuki, Atsushi; Palmer, Gaby; Bonjour, Jean Philippe; Caverzasio, Joseph.

In: Journal of Bone and Mineral Research, Vol. 15, No. 1, 01.01.2000, p. 95-102.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Stimulation of sodium-dependent phosphate transport and signaling mechanisms induced by basic fibroblast growth factor in MC3T3-E1 osteoblast- like cells

AU - Suzuki, Atsushi

AU - Palmer, Gaby

AU - Bonjour, Jean Philippe

AU - Caverzasio, Joseph

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N2 - 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.

AB - 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.

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