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Inhibitory regulation of osteogenesis in sutures of mammalian skull

哺乳动物颅骨缝合线成骨的抑制调节

基本信息

批准号：
15390554
负责人：
ISEKI Sachiko
金额：
$ 9.41万
依托单位：
Tokyo Medical and Dental University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

Molecular mechanism of formation and maintenance of calvarial sutures was investigated. Our study suggests that spatio- temporal expression of various molecules in different tissues is required for suture formation and suture maintenance.During suture formation, a basic helix-loop-helix type transcription factor, Twist 1, is required for cell proliferation of sutural mesenchyme and regulation of undifferentiated condition of preosteoblast at the periphery of the developing skull bone. Meningeal layer regulates the growth of the overlying calvarial bone and we found that bone morphogenetic protein signals play partly in this process. Fibroblast growth factor (FGF) receptors are preferentially expressed in osteoblast cell lineage and enhanced FGF signaling is responsible for acceleration of osteogenesis, which leads to immature fusion of the suture. We found that application of different FGF-soaked beads cause different reaction in fetal mouse coronal suture, FGF-soaked beads induced expression of osteogenic markers but induction of mineralization depends on which FGF was applied. We are now currently trying to explain this difference using combination of downstream molecules of Fgf signaling.Periodontal ligament also maintains fibroblastic condition in response to occlusal force. Formation of the periodontal ligament is closely associated with tooth root formation. We have therefore investigated tooth root formation. We found that sonic hedgehog signaling is required for root elongation but it does not regulate the formation of the periodontal ligament. In contrast, Fgf signaling appears to be involved in ligament formation as well as root formation. FGF beads application onto the crown formed tooth buds grafted in kidney capsule also showed different consequence on root formation depends on which FGF was used. Based on these observations we plan to investigate functions of Fgf signaling in periodontal tissue formation including teeth.

探讨了颅骨缝合线形成和维持的分子机制。我们的研究表明，不同组织中不同分子的时空表达是缝线形成和缝线维持所必需的。在缝合形成过程中，一种基本的螺旋-环-螺旋型转录因子Twist 1在发育中的颅骨周围的缝合间质细胞增殖和成骨前细胞未分化状态的调节中发挥着重要作用。脑膜层调节上覆颅骨的生长，我们发现骨形态发生蛋白信号在这一过程中起部分作用。成纤维细胞生长因子（FGF）受体在成骨细胞谱系中优先表达，FGF信号的增强负责加速成骨，从而导致缝合线的未成熟融合。我们发现不同的FGF浸泡珠粒在胎鼠冠状缝合中引起不同的反应，FGF浸泡珠粒诱导成骨标志物的表达，但诱导矿化取决于使用哪种FGF。我们目前正试图利用Fgf信号的下游分子组合来解释这种差异。牙周韧带在咬合力的作用下也能维持成纤维状态。牙周韧带的形成与牙根的形成密切相关。因此，我们研究了牙根的形成。我们发现超音hedgehog基因信号是牙根伸长所必需的，但它不调节牙周韧带的形成。相反，Fgf信号似乎参与韧带的形成和根的形成。在肾包膜内移植的冠状牙芽上应用FGF珠粒对根的形成也有不同的影响。基于这些观察结果，我们计划研究Fgf信号在牙周组织形成（包括牙齿）中的功能。