Activation of the FGF signaling pathway and subsequent induction of mesenchymal stem cell differentiation by inorganic polyphosphate
<p>Inorganic polyphosphate [poly(P)] is a biopolymer existing in almost all cells and tissues, although its biological functions in higher eukaryotes have not been completely elucidated. We previously demonstrated that poly(P) enhances the function of fibroblast growth factors (FGFs) by stabil...
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Format: | Article |
Language: | English |
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Ivyspring International Publisher
2008-01-01
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Series: | International Journal of Biological Sciences |
Online Access: | http://www.biolsci.org/v04p0037.htm |
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author | Yumi Kawazoe, Shinichi Katoh, Yuichiro Onodera, Takao Kohgo, Masanobu Shindoh, Toshikazu Shiba |
author_facet | Yumi Kawazoe, Shinichi Katoh, Yuichiro Onodera, Takao Kohgo, Masanobu Shindoh, Toshikazu Shiba |
author_sort | Yumi Kawazoe, Shinichi Katoh, Yuichiro Onodera, Takao Kohgo, Masanobu Shindoh, Toshikazu Shiba |
collection | DOAJ |
description | <p>Inorganic polyphosphate [poly(P)] is a biopolymer existing in almost all cells and tissues, although its biological functions in higher eukaryotes have not been completely elucidated. We previously demonstrated that poly(P) enhances the function of fibroblast growth factors (FGFs) by stabilizing them and strengthening the affinity between FGFs and their cell surface receptors. Since FGFs play crucial roles in bone regeneration, we further investigated the effect of poly(P) on the cell differentiation of human stem cells via FGF signaling systems. Human dental pulp cells (HDPCs) isolated from human dental pulp show the characteristics of multipotent mesenchymal stem cells (MSCs). HDPCs secreted FGFs and the proliferation of HDPCs was shown to be enhanced by treatment with poly(P). Cell surface receptor-bound FGF-2 was stably maintained for more than 40 hours in the presence of poly(P). The phosphorylation of ERK1/2 was also enhanced by poly(P). The effect of poly(P) on the osteogenic differentiation of HDPCs and human MSCs (hMSCs) were also investigated. After 5 days of treatment with poly(P), type-I collagen expression of both cell types was enhanced. The C-terminal peptide of type-I collagen was also released at higher levels in poly(P)-treated HDPCs. Microarray analysis showed that expression of matrix metalloproteinase-1 (MMP1), osteopontin (OPN), osteocalcin (OC) and osteoprotegerin was induced in both cell types by poly(P). Furthermore, induced expression of MMP1, OPN and OC genes in both cells was confirmed by real-time PCR. Calcification of both cell types was clearly observed by alizarin red staining following treatment with poly(P). The results suggest that the activation of the FGF signaling pathway by poly(P) induces both proliferation and mineralization of stem cells.</p> |
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format | Article |
id | doaj.art-2aa262af54a641fc849890fa8b67c48d |
institution | Directory Open Access Journal |
issn | 1449-2288 |
language | English |
last_indexed | 2024-04-12T10:50:48Z |
publishDate | 2008-01-01 |
publisher | Ivyspring International Publisher |
record_format | Article |
series | International Journal of Biological Sciences |
spelling | doaj.art-2aa262af54a641fc849890fa8b67c48d2022-12-22T03:36:14ZengIvyspring International PublisherInternational Journal of Biological Sciences1449-22882008-01-01413747Activation of the FGF signaling pathway and subsequent induction of mesenchymal stem cell differentiation by inorganic polyphosphateYumi Kawazoe, Shinichi Katoh, Yuichiro Onodera, Takao Kohgo, Masanobu Shindoh, Toshikazu Shiba<p>Inorganic polyphosphate [poly(P)] is a biopolymer existing in almost all cells and tissues, although its biological functions in higher eukaryotes have not been completely elucidated. We previously demonstrated that poly(P) enhances the function of fibroblast growth factors (FGFs) by stabilizing them and strengthening the affinity between FGFs and their cell surface receptors. Since FGFs play crucial roles in bone regeneration, we further investigated the effect of poly(P) on the cell differentiation of human stem cells via FGF signaling systems. Human dental pulp cells (HDPCs) isolated from human dental pulp show the characteristics of multipotent mesenchymal stem cells (MSCs). HDPCs secreted FGFs and the proliferation of HDPCs was shown to be enhanced by treatment with poly(P). Cell surface receptor-bound FGF-2 was stably maintained for more than 40 hours in the presence of poly(P). The phosphorylation of ERK1/2 was also enhanced by poly(P). The effect of poly(P) on the osteogenic differentiation of HDPCs and human MSCs (hMSCs) were also investigated. After 5 days of treatment with poly(P), type-I collagen expression of both cell types was enhanced. The C-terminal peptide of type-I collagen was also released at higher levels in poly(P)-treated HDPCs. Microarray analysis showed that expression of matrix metalloproteinase-1 (MMP1), osteopontin (OPN), osteocalcin (OC) and osteoprotegerin was induced in both cell types by poly(P). Furthermore, induced expression of MMP1, OPN and OC genes in both cells was confirmed by real-time PCR. Calcification of both cell types was clearly observed by alizarin red staining following treatment with poly(P). The results suggest that the activation of the FGF signaling pathway by poly(P) induces both proliferation and mineralization of stem cells.</p>http://www.biolsci.org/v04p0037.htm |
spellingShingle | Yumi Kawazoe, Shinichi Katoh, Yuichiro Onodera, Takao Kohgo, Masanobu Shindoh, Toshikazu Shiba Activation of the FGF signaling pathway and subsequent induction of mesenchymal stem cell differentiation by inorganic polyphosphate International Journal of Biological Sciences |
title | Activation of the FGF signaling pathway and subsequent induction of mesenchymal stem cell differentiation by inorganic polyphosphate |
title_full | Activation of the FGF signaling pathway and subsequent induction of mesenchymal stem cell differentiation by inorganic polyphosphate |
title_fullStr | Activation of the FGF signaling pathway and subsequent induction of mesenchymal stem cell differentiation by inorganic polyphosphate |
title_full_unstemmed | Activation of the FGF signaling pathway and subsequent induction of mesenchymal stem cell differentiation by inorganic polyphosphate |
title_short | Activation of the FGF signaling pathway and subsequent induction of mesenchymal stem cell differentiation by inorganic polyphosphate |
title_sort | activation of the fgf signaling pathway and subsequent induction of mesenchymal stem cell differentiation by inorganic polyphosphate |
url | http://www.biolsci.org/v04p0037.htm |
work_keys_str_mv | AT yumikawazoeshinichikatohyuichiroonoderatakaokohgomasanobushindohtoshikazushiba activationofthefgfsignalingpathwayandsubsequentinductionofmesenchymalstemcelldifferentiationbyinorganicpolyphosphate |