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Activation of the FGF signaling pathway and subsequent induction of mesenchymal stem cell differentiation by inorganic polyphosphate.

Kawazoe Y, Katoh S, Onodera Y, Kohgo T, Shindoh M, Shiba T - Int. J. Biol. Sci. (2008)

Bottom Line: The effect of poly(P) on the osteogenic differentiation of HDPCs and human MSCs (hMSCs) were also investigated.Furthermore, induced expression of MMP1, OPN and OC genes in both cells was confirmed by real-time PCR.The results suggest that the activation of the FGF signaling pathway by poly(P) induces both proliferation and mineralization of stem cells.

View Article: PubMed Central - PubMed

Affiliation: Regenetiss Inc., 1-9-4, Asahigaoka, Hino, Tokyo 191-0065, Japan.

ABSTRACT
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.

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Acceleration of cell calcification by poly(P). Time course of calcification in HDPCs and hMSCs during poly(P) treatment. HDPCs and hMSCs were treated with 1 mM poly(P) for 34 and 24 days, respectively. Non-treated HDPCs and hMSCs (None) cultured for 34 and 24 days, respectively, were also stained with alizarin red.
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Figure 6: Acceleration of cell calcification by poly(P). Time course of calcification in HDPCs and hMSCs during poly(P) treatment. HDPCs and hMSCs were treated with 1 mM poly(P) for 34 and 24 days, respectively. Non-treated HDPCs and hMSCs (None) cultured for 34 and 24 days, respectively, were also stained with alizarin red.

Mentions: To visualize calcium deposition and cell calcification, both HDPCs and hMSCs were stained by alizarin red. As shown in Fig. 6, HDPCs and hMSCs treated with poly(P) showed visible calcium deposition after the addition of poly(P), whereas no calcification was observed in non-treated cells. The level of calcium deposition increased at 20 and 17 days after poly(P) treatment in HDPCs and hMSCs, respectively. Calcification reached a maximum level at around 34 to 24 days after the start of poly(P) treatment in HDPCs and hMSCs, respectively.


Activation of the FGF signaling pathway and subsequent induction of mesenchymal stem cell differentiation by inorganic polyphosphate.

Kawazoe Y, Katoh S, Onodera Y, Kohgo T, Shindoh M, Shiba T - Int. J. Biol. Sci. (2008)

Acceleration of cell calcification by poly(P). Time course of calcification in HDPCs and hMSCs during poly(P) treatment. HDPCs and hMSCs were treated with 1 mM poly(P) for 34 and 24 days, respectively. Non-treated HDPCs and hMSCs (None) cultured for 34 and 24 days, respectively, were also stained with alizarin red.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2238184&req=5

Figure 6: Acceleration of cell calcification by poly(P). Time course of calcification in HDPCs and hMSCs during poly(P) treatment. HDPCs and hMSCs were treated with 1 mM poly(P) for 34 and 24 days, respectively. Non-treated HDPCs and hMSCs (None) cultured for 34 and 24 days, respectively, were also stained with alizarin red.
Mentions: To visualize calcium deposition and cell calcification, both HDPCs and hMSCs were stained by alizarin red. As shown in Fig. 6, HDPCs and hMSCs treated with poly(P) showed visible calcium deposition after the addition of poly(P), whereas no calcification was observed in non-treated cells. The level of calcium deposition increased at 20 and 17 days after poly(P) treatment in HDPCs and hMSCs, respectively. Calcification reached a maximum level at around 34 to 24 days after the start of poly(P) treatment in HDPCs and hMSCs, respectively.

Bottom Line: The effect of poly(P) on the osteogenic differentiation of HDPCs and human MSCs (hMSCs) were also investigated.Furthermore, induced expression of MMP1, OPN and OC genes in both cells was confirmed by real-time PCR.The results suggest that the activation of the FGF signaling pathway by poly(P) induces both proliferation and mineralization of stem cells.

View Article: PubMed Central - PubMed

Affiliation: Regenetiss Inc., 1-9-4, Asahigaoka, Hino, Tokyo 191-0065, Japan.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus