Document Detail

FGF2 stimulation of the pyrophosphate-generating enzyme, PC-1, in pre-osteoblast cells is mediated by RUNX2.
MedLine Citation:
PMID:  19049325     Owner:  NLM     Status:  MEDLINE    
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.
Nan E Hatch; Yan Li; Renny T Franceschi
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research     Volume:  24     ISSN:  1523-4681     ISO Abbreviation:  J. Bone Miner. Res.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-01     Completed Date:  2009-07-16     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  8610640     Medline TA:  J Bone Miner Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  652-62     Citation Subset:  IM    
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MeSH Terms
Binding Sites
Bone Marrow Cells / cytology,  drug effects,  enzymology
Carrier Proteins / metabolism
Cell Nucleus / drug effects,  metabolism
Core Binding Factor Alpha 1 Subunit / metabolism*
Diphosphates / metabolism*
Dose-Response Relationship, Drug
Fibroblast Growth Factor 2 / pharmacology*
Membrane Proteins / metabolism
Mutation / genetics
Osteoblasts / cytology,  drug effects*,  enzymology*
Phosphate Transport Proteins
Phosphoric Diester Hydrolases / genetics,  metabolism*
Promoter Regions, Genetic / genetics
Protein Binding / drug effects
Protein Transport / drug effects
Pyrophosphatases / genetics,  metabolism*
Skull / cytology,  enzymology
Stromal Cells / drug effects,  enzymology
Time Factors
Transcription, Genetic / drug effects
Grant Support
Reg. No./Substance:
0/Carrier Proteins; 0/Core Binding Factor Alpha 1 Subunit; 0/Diphosphates; 0/Membrane Proteins; 0/Phosphate Transport Proteins; 0/ank protein, mouse; 103107-01-3/Fibroblast Growth Factor 2; EC 3.1.4.-/Phosphoric Diester Hydrolases; EC pyrophosphatase phosphodiesterase 1; EC 3.6.1.-/Pyrophosphatases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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