FGF2 Stimulation of the Pyrophosphate-Generating Enzyme, PC-1, in Pre-Osteoblast Cells Is Mediated by RUNX2
FGF2 Stimulation of the Pyrophosphate-Generating Enzyme, PC-1, in Pre-Osteoblast Cells Is Mediated by RUNX2
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DOI：
10.1359/jbmr.081213
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发表时间：
2009-04-01
影响因子：
6.2
通讯作者：
Franceschi, Renny T.
中科院分区：
文献类型：
--
作者：
Hatch, Nan E.;Li, Yan;Franceschi, Renny T.
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 preosteoblast cells and that FGF2 induces PC-1 expression through a mechanism involving Runx2.
