Cooperative Effects of FGF-2 and VEGF-A in Periodontal Ligament Cells
Cooperative Effects of FGF-2 and VEGF-A in Periodontal Ligament Cells
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DOI：
10.1177/0022034513511640
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发表时间：
2014-01-01
影响因子：
7.6
通讯作者：
Murakami, S.
中科院分区：
文献类型：
--
作者：
Yanagita, M.;Kojima, Y.;Murakami, S.
我们以前证明，局部应用成纤维细胞生长因子（FGF）-2增强牙周组织再生。虽然血管生成是组织再生的关键事件，但局部应用FGF-2诱导牙周组织血管生成的机制尚未完全阐明。在这项研究中，我们调查是否FGF-2可以诱导血管内皮生长因子（VEGF）-A在牙周膜（PDL）细胞的表达，以及PDL细胞和内皮细胞之间的细胞间相互作用是否可以刺激血管生成。FGF-2以剂量依赖性方式诱导MPDL 22细胞（小鼠牙周膜细胞系）分泌VEGF-A。Transwell和伤口愈合试验显示，FGF-2加VEGF-A的共刺激协同刺激MPDL 22细胞的迁移。有趣的是，MPDL 22细胞与bEnd 5细胞（小鼠内皮细胞系）的共培养也刺激了MPDL 22细胞的VEGF-A产生和bEnd 5细胞的管形成。此外，延时分析显示，MPDL 22细胞迁移接近管形成bEnd 5细胞，模仿周细胞。因此，FGF-2诱导PDL细胞中的VEGF-A表达，并与VEGF-A组合诱导血管生成。与PDL细胞的细胞间相互作用也促进血管生成。
We previously demonstrated that topical application of fibroblast growth factor (FGF)-2 enhanced periodontal tissue regeneration. Although angiogenesis is a crucial event for tissue regeneration, the mechanism(s) by which topically applied FGF-2 induces angiogenesis in periodontal tissues has not been fully clarified. In this study, we investigated whether FGF-2 could induce vascular endothelial growth factor (VEGF)-A expression in periodontal ligament (PDL) cells and whether cell-to-cell interactions between PDL cells and endothelial cells could stimulate angiogenesis. FGF-2 induced VEGF-A secretion from MPDL22 cells (mouse periodontal ligament cell line) in a dose-dependent manner. Transwell and wound-healing assays revealed that co-stimulation with FGF-2 plus VEGF-A synergistically stimulated the migration of MPDL22 cells. Interestingly, co-culture of MPDL22 cells with bEnd5 cells (mouse endothelial cell line) also stimulated VEGF-A production from MPDL22 cells and tube formation by bEnd5 cells. Furthermore, time-lapse analysis revealed that MPDL22 cells migrated close to the tube-forming bEnd5 cells, mimicking pericytes. Thus, FGF-2 induces VEGF-A expression in PDL cells and induces angiogenesis in combination with VEGF-A. Cell-to-cell interactions with PDL cells also facilitate angiogenesis.