Activation of the FGF signaling pathway and subsequent induction of mesenchymal stem cell differentiation by inorganic polyphosphate.
Activation of the FGF signaling pathway and subsequent induction of mesenchymal stem cell differentiation by inorganic polyphosphate.
复制标题
FGF信号通路的激活以及随后通过无机多磷酸盐诱导间充质干细胞分化的激活。
DOI：
10.7150/ijbs.4.37
复制
发表时间：
2008-02-03
影响因子：
9.2
通讯作者：
Shiba, Toshikazu
中科院分区：
文献类型：
--
作者：
Kawazoe, Yumi;Katoh, Shinichi;Onodera, Yuichiro;Kohgo, Takao;Shindoh, Masanobu;Shiba, Toshikazu
关键词：
无机多聚磷酸盐[poly（P）]是一种存在于几乎所有细胞和组织中的生物聚合物，但其在高等真核生物中的生物学功能尚未完全阐明。我们以前证明，聚（P）通过稳定成纤维细胞生长因子（FGF）和增强FGF与其细胞表面受体之间的亲和力来增强FGF的功能。由于FGF在骨再生中起着至关重要的作用，我们进一步研究了poly（P）通过FGF信号系统对人干细胞的细胞分化的影响。人牙髓细胞（HDPCs）是从人牙髓中分离的具有多潜能间充质干细胞（MSCs）特性的细胞。HDPC分泌FGF，并且显示用聚（P）处理HDPC的增殖增强。细胞表面受体结合的FGF-2在聚（P）存在下稳定维持超过40小时。poly（P）对ERK 1/2的磷酸化也有促进作用。同时观察了poly（P）对HDPCs和人骨髓间充质干细胞（hMSCs）成骨分化的影响。在用聚（P）处理5天后，两种细胞类型的I型胶原表达增强。在poly（P）处理的HDPCs中，I型胶原的C-末端肽也以更高的水平释放。基因芯片分析显示，聚（P）可诱导两种细胞表达基质金属蛋白酶1（MMP 1）、骨桥蛋白（OPN）、骨钙素（OC）和骨保护素。此外，通过实时PCR证实两种细胞中MMP 1、OPN和OC基因的诱导表达。用聚（P）处理后，通过茜素红染色清楚地观察到两种细胞类型的钙化。结果表明，聚（P）激活FGF信号通路诱导干细胞的增殖和矿化。
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.
登录
查看更多内容
影响因子：
7.8
作者：
ASAHINA, I;SAMPATH, TK;HAUSCHKA, PV
通讯作者：
HAUSCHKA, PV
影响因子：
4.8
作者：
Shiba, T;Nishimura, D;Ohshiro, M
通讯作者：
Ohshiro, M
影响因子：
4.8
作者：
KUMBLE, KD;KORNBERG, A
通讯作者：
KORNBERG, A
影响因子：
7.6
作者：
Hacchou, Y.;Uematsu, T.;Furusawa, K.
通讯作者：
Furusawa, K.
影响因子：
4.8
作者：
Kwan, CP;Venkataraman, G;Sasisekharan, R
通讯作者：
Sasisekharan, R