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FGF2 alters expression of the pyrophosphate/phosphate regulating proteins, PC-1, ANK and TNAP, in the calvarial osteoblastic cell line, MC3T3E1(C4).
Connect Tissue Res. 2005; 46(4-5):184-92.CT

Abstract

Fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling has been linked to the aberrant mineralization phenotype of craniosynostosis syndromes. One critical aspect of mineralization involves the elaboration and transport of pyrophosphate into the extracellular matrix with subsequent enzymatic hydrolysis into phosphate. Altered expression of the pyrophosphate elaborating factors, TNAP (tissue nonspecific alkaline phosphatase), PC-1, and ANK, downstream of FGF/FGFR signaling may provide a potential mechanism for the craniosynostosis phenotype. As an initial step toward testing this hypothesis, we confirmed that ANK mRNA is upregulated during osteoblast differentiation in culture. Subsequently, the effect of FGF2 treatment on expression of PC-1, ANK, and TNAP in the calvarial osteoblastic cell line, MC3T3E1(C4), was investigated. FGF2 specifically induced expression of PC-1 and ANK while inhibiting expression of TNAP, at both mRNA and protein levels. Concordant with these changes in gene expression, FGF2 inhibited mineralization. These results suggest that FGF/FGFR signaling may affect mineralization via changes in the elaboration and metabolism of pyrophosphate.

Authors+Show Affiliations

Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195, USA. nhatch@u.washington.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16546821

Citation

Hatch, Nan E., et al. "FGF2 Alters Expression of the Pyrophosphate/phosphate Regulating Proteins, PC-1, ANK and TNAP, in the Calvarial Osteoblastic Cell Line, MC3T3E1(C4)." Connective Tissue Research, vol. 46, no. 4-5, 2005, pp. 184-92.
Hatch NE, Nociti F, Swanson E, et al. FGF2 alters expression of the pyrophosphate/phosphate regulating proteins, PC-1, ANK and TNAP, in the calvarial osteoblastic cell line, MC3T3E1(C4). Connect Tissue Res. 2005;46(4-5):184-92.
Hatch, N. E., Nociti, F., Swanson, E., Bothwell, M., & Somerman, M. (2005). FGF2 alters expression of the pyrophosphate/phosphate regulating proteins, PC-1, ANK and TNAP, in the calvarial osteoblastic cell line, MC3T3E1(C4). Connective Tissue Research, 46(4-5), 184-92.
Hatch NE, et al. FGF2 Alters Expression of the Pyrophosphate/phosphate Regulating Proteins, PC-1, ANK and TNAP, in the Calvarial Osteoblastic Cell Line, MC3T3E1(C4). Connect Tissue Res. 2005;46(4-5):184-92. PubMed PMID: 16546821.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - FGF2 alters expression of the pyrophosphate/phosphate regulating proteins, PC-1, ANK and TNAP, in the calvarial osteoblastic cell line, MC3T3E1(C4). AU - Hatch,Nan E, AU - Nociti,Francisco, AU - Swanson,Erica, AU - Bothwell,Mark, AU - Somerman,Martha, PY - 2006/3/21/pubmed PY - 2006/4/15/medline PY - 2006/3/21/entrez SP - 184 EP - 92 JF - Connective tissue research JO - Connect. Tissue Res. VL - 46 IS - 4-5 N2 - Fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling has been linked to the aberrant mineralization phenotype of craniosynostosis syndromes. One critical aspect of mineralization involves the elaboration and transport of pyrophosphate into the extracellular matrix with subsequent enzymatic hydrolysis into phosphate. Altered expression of the pyrophosphate elaborating factors, TNAP (tissue nonspecific alkaline phosphatase), PC-1, and ANK, downstream of FGF/FGFR signaling may provide a potential mechanism for the craniosynostosis phenotype. As an initial step toward testing this hypothesis, we confirmed that ANK mRNA is upregulated during osteoblast differentiation in culture. Subsequently, the effect of FGF2 treatment on expression of PC-1, ANK, and TNAP in the calvarial osteoblastic cell line, MC3T3E1(C4), was investigated. FGF2 specifically induced expression of PC-1 and ANK while inhibiting expression of TNAP, at both mRNA and protein levels. Concordant with these changes in gene expression, FGF2 inhibited mineralization. These results suggest that FGF/FGFR signaling may affect mineralization via changes in the elaboration and metabolism of pyrophosphate. SN - 0300-8207 UR - https://www.unboundmedicine.com/medline/citation/16546821/FGF2_alters_expression_of_the_pyrophosphate/phosphate_regulating_proteins_PC_1_ANK_and_TNAP_in_the_calvarial_osteoblastic_cell_line_MC3T3E1_C4__ L2 - http://www.tandfonline.com/doi/full/10.1080/03008200500237203 DB - PRIME DP - Unbound Medicine ER -