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FGF2 Stimulation of the Pyrophosphate‐Generating Enzyme, PC‐1, in Pre‐Osteoblast Cells Is Mediated by RUNX2
Author(s) -
Hatch Nan E,
Li Yan,
Franceschi Renny T
Publication year - 2009
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.081213
Subject(s) - runx2 , osteoblast , pyrophosphate , alkaline phosphatase , transfection , chemistry , microbiology and biotechnology , chromatin immunoprecipitation , biochemistry , biology , gene expression , enzyme , promoter , in vitro , gene
Pyrophosphate is an established inhibitor of hydroxyapatite deposition and crystal growth, yet when hydrolyzed into phosphate, it becomes a substrate for hydroxyapatite deposition. Pyrophosphate‐generating enzyme (PC‐1), Ank, and tissue nonspecific alkaline phosphatase (Tnap) are three factors that regulate extracellular pyrophosphate levels through its generation, transport, and hydrolysis. We previously showed that fibroblast growth factor 2 (FGF2) induces PC‐1 and Ank while inhibiting Tnap expression and mineralization in MC3T3E1(C4) calvarial pre‐osteoblast cells. In this study, we showed similar FGF2 regulation of these genes in primary pre‐osteoblast cultures. In contrast to Ank and Tnap that are regulated by FGF2 in multiple cell types, we found regulation of PC‐1 to be selective to pre‐osteoblastic cells and to require the osteoblast‐related transcription factor, Runx2. Specifically, FGF2 was unable to induce PC‐1 expression in Runx2‐negative nonbone cells or in calvarial cells from Runx2‐deficient mice. Transfection of these cells with a Runx2 expression vector restored FGF2 responsiveness. FGF2 was also shown to stimulate recruitment of Runx2 to the endogenous PC‐1 promoter in MC3T3E1(C4) cells, as measured by chromatin immunoprecipitation. Taken together, our results establish that FGF2 is a specific inducer of PC‐1 in pre‐osteoblast cells and that FGF2 induces PC‐1 expression through a mechanism involving Runx2.