Effects of VEGF and FGF-2 on proliferation and differentiation of human periodontal ligament stem cells
Effects of VEGF and FGF-2 on proliferation and differentiation of human periodontal ligament stem cells
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DOI：
10.1007/s00441-012-1392-x
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发表时间：
2012-06-01
影响因子：
3.6
通讯作者：
Seo, Byoung Moo
中科院分区：
文献类型：
--
作者：
Lee, Joo-Hee;Um, Soyoun;Seo, Byoung Moo
人离体第三磨牙牙周膜干细胞是一种来源于牙体组织的成体干细胞。已知PDLSC具有自我更新能力和多谱系分化潜力。血管内皮生长因子（VEGF）是一种血管生成因子，可刺激内皮细胞有丝分裂和细胞迁移。另一种生长因子，成纤维细胞生长因子-2（FGF-2），一种促有丝分裂因子，增强间充质干细胞（MSC）中的骨生成。本研究探讨VEGF和FGF-2对PDLSCs在体外和体内的影响，与骨髓干细胞（BMSCs）作为阳性对照。用VEGF处理PDLSC增加了钙结节的积累、碱性磷酸酶（ALP）活性和硬组织的形成，并上调了runt相关转录因子2（Runx 2）的mRNA水平。相比之下，FGF-2在体外细胞培养中增强PDLSC的增殖，其中它显著降低钙积累和ALP活性并下调成骨基因标志物（即，Runx 2、ALP、I型胶原）参与成骨诱导。我们还将具有羟基磷灰石/磷酸三钙颗粒（HA/TCP）作为每个因子（VEGF、FGF-2）的载体的PDLSC移植到裸鼠中，8周后，观察在背部表面的硬组织的体内形成。基于我们的研究结果，我们认为VEGF在体外对牙/成骨分化和体内矿化结构的形成具有积极作用。FGF-2可能是硬组织再生中祖细胞增殖的有力促进剂，但外源性FGF-2可能抑制终末分化。
Human periodontal ligament stem cells (PDLSCs) from extracted third molar teeth are a type of adult stem cell originating from dental tissue. PDLSCs are known to have a self-renewal capacity and multi-lineage differentiation potential. Vascular endothelial growth factor (VEGF), an angiogenic/vasculogenic factor, has been shown to stimulate endothelial cell mitogenesis and cell migration. Another growth factor, fibroblast growth factor-2 (FGF-2), a mitogenic factor, enhances osteogenesis in mesenchymal stem cells (MSCs). This study examines the effects of VEGF and FGF-2 on PDLSCs in vitro and in vivo compared with those on bone marrow stem cells (BMSCs) as a positive control. Treatment of PDLSCs with VEGF increases the accumulation of calcium nodules, alkaline phosphatase (ALP) activity and the formation of hard tissue and up-regulates the mRNA level of runt-related transcription factor 2 (Runx2). In contrast, FGF-2 enhances the proliferation of PDLSCs in vitro in cell culture, where it significantly decreases calcium accumulation and ALP activity and down-regulates the expression of osteogenic gene markers (i.e., Runx2, ALP, type I collagen) involved in osteogenic induction. We have also transplanted PDLSCs with hydroxyapatite/tricalcium phosphate particles (HA/TCP) as carriers for each factor (VEGF, FGF-2) into nude mice and, after 8 weeks, observed the in vivo formation of hard tissue at the dorsal surface. Based on our results, we suggest that VEGF has positive effects on odonto-/osteogenic differentiation in vitro and on the formation of mineralized structure in vivo. FGF-2 might be a powerful promoter of the proliferation of progenitor cells in hard tissue regeneration but exogenous FGF-2 might inhibit terminal differentiation.