Lovschall Henrik, Mitsiadis Thimios A, Poulsen Knud, Jensen Kristina H, Kjeldsen Annette L
Department of Dental Pathology, Operative Dentistry and Endodontics, Royal Dental College, Faculty of Health Sciences, University of Aarhus, DK-8000 Aarhus C, Denmark.
Int J Dev Biol. 2007;51(8):715-21. doi: 10.1387/ijdb.072393hl.
Recent studies have shown that the pulp of human teeth contains a population of cells with stem cell properties and it has been suggested that these cells originate from pericytes. Molecules of the Notch signaling pathway regulate stem cell fate specification, while Rgs5 represents an excellent marker for pericytes. Pathological conditions such as dental trauma and carious lesion stimulate pulp stem cells to elaborate reparative dentin. Previous studies have shown that genes involved in the Notch pathway are activated in response to pulp injury in rodent and humans. To demonstrate the importance of pericytes as a source of stem cells during dental repair, we have studied Rgs5 and Notch3 mRNA expression by in situ hybridization in developing, adult intact and injured rodent teeth. Furthermore, we have examined the distribution of Notch3 protein in carious and injured human teeth using immunohistochemistry. Overlapping expression patterns of Rgs5 and Notch3 were observed during rodent tooth development as well as immediately after injury. Both genes were expressed in vascular structures during development and in perivascular and single capillary cells of injured teeth. However, the expression patterns of Rgs5 and Notch3 were different during tooth repair, with relatively extensive Rgs5 expression along the pericyte-vascular smooth muscle cell axis in central pulp arterioles. These results show co-expression of Rgs5 and Notch3 in pericytes of developing and injured teeth and furthermore indicate the importance of vascular-derived stem cells during pulp healing.
最近的研究表明,人类牙髓中含有一群具有干细胞特性的细胞,有人认为这些细胞起源于周细胞。Notch信号通路的分子调节干细胞命运的决定,而Rgs5是周细胞的一个优秀标志物。诸如牙齿外伤和龋损等病理状况会刺激牙髓干细胞生成修复性牙本质。先前的研究表明,在啮齿动物和人类中,Notch通路相关基因在牙髓损伤后会被激活。为了证明周细胞作为牙齿修复过程中干细胞来源的重要性,我们通过原位杂交研究了发育中的、成年完整的和受伤的啮齿动物牙齿中Rgs5和Notch3 mRNA的表达。此外,我们使用免疫组织化学检查了Notch3蛋白在龋损和受伤人类牙齿中的分布。在啮齿动物牙齿发育过程中以及损伤后立即观察到Rgs5和Notch3的重叠表达模式。在发育过程中,这两个基因均在血管结构中表达,在受伤牙齿的血管周围细胞和单个毛细血管细胞中也有表达。然而,在牙齿修复过程中,Rgs5和Notch3的表达模式不同,在中央牙髓小动脉的周细胞 - 血管平滑肌细胞轴上,Rgs5表达相对广泛。这些结果表明,Rgs5和Notch3在发育中和受伤牙齿的周细胞中共表达,并且进一步表明血管源性干细胞在牙髓愈合过程中的重要性。