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We previously reported that elevated extracellular calcium (Ca 2+ ) levels increase bone morphogenetic protein 2 expression in human dental pulp (hDP) cells. However, it is unknown whether extracellular Ca 2+  affects the expression of other growth factors such as fibroblast growth factor 2 (FGF2).   Objective:  The present study aimed to examine the effect of extracellular Ca 2+  on FGF2 gene expression in hDP and immortalized mouse dental papilla (mDP) cells.    Materials and Methods:  Cells were stimulated with 10 mM CaCl 2  in the presence or absence of cell signaling inhibitors. FGF2 gene expression was assessed using real-time polymerase chain reaction. The phosphorylation status of signaling molecules was examined by Western blotting.    Results:  Extracellular Ca 2+  increased FGF2 gene expression in mDP and hDP cells. Gene expression of the calcium-sensing receptor and G protein-coupled receptor family C group 6 member A, both of which are extracellular Ca 2+  sensors, was not detected. Ca 2+ -mediated  Fgf2  expression was reduced by pretreatment with the protein kinase A (PKA) inhibitor H-89 or extracellular signal-regulated kinase (ERK) 1/2 inhibitor PD98059 but not by pretreatment with the protein kinase C inhibitor GF-109203X or p38 inhibitor SB203580. Extracellular Ca 2+  increased PKA activity and ERK1/2 phosphorylation. Ca 2+ -induced PKA activity decreased by pretreatment with PD98059.    Conclusions:  These findings indicate that elevated extracellular Ca 2+  levels led to increased  Fgf2  expression through ERK1/2 and PKA in mDP cells and that this mechanism may be useful for designing regenerative therapies for dentin.

journal of applied oral science

Extracellular calcium increases fibroblast growth factor 2 gene expression via extracellular signal-regulated kinase 1/2 and protein kinase A signaling in mouse dental papilla cells