Mitsiadis Thimios A, Catón Javier, Pagella Pierfrancesco, Orsini Giovanna, Jimenez-Rojo Lucia
Orofacial Development and Regeneration, Faculty of Medicine, Institute of Oral Biology, ZZM, University of ZurichZurich, Switzerland.
Department of Medical Basic Sciences, Faculty of Medicine, University CEU-San PabloMadrid, Spain.
Front Physiol. 2017 May 30;8:372. doi: 10.3389/fphys.2017.00372. eCollection 2017.
Dental pulp stem/progenitor cells guarantee tooth homeostasis, repair and regeneration throughout life. The decision between renewal and differentiation of these cells is influenced by physical and molecular interactions with stromal cells and extracellular matrix molecules forming the specialized microenvironment of dental pulp stem cell niches. Here we study the activation of putative pulp niches after tooth injury through the upregulation of Notch signaling pathway. Notch1, Notch2, and Notch3 molecules were used as markers of dental pulp stem/progenitor cells. Upon dental injury, Notch1 and Notch3 are detected in cells related to vascular structures suggesting a role of these proteins in the activation of specific pulpal perivascular niches. In contrast, a population of Notch2-positive cells that are actively proliferative is observed in the apical part of the pulp. Kinetics of these cells is followed up with a lipophilic DiI labeling, showing that apical pulp cells migrate toward the injury site where dynamic regenerative/repair events occur. The knowledge of the activation and regulation of dental pulp stem/progenitor cells within their niches in pathologic conditions may be helpful for the realization of innovative dental treatments in the near future.
牙髓干细胞/祖细胞在整个生命过程中维持牙齿的内环境稳定、修复和再生。这些细胞更新与分化之间的抉择受与基质细胞及细胞外基质分子的物理和分子相互作用影响,这些细胞和分子构成了牙髓干细胞龛的特殊微环境。在此,我们通过Notch信号通路的上调来研究牙齿损伤后假定牙髓龛的激活情况。Notch1、Notch2和Notch3分子用作牙髓干细胞/祖细胞的标志物。牙齿损伤后,在与血管结构相关的细胞中检测到Notch1和Notch3,提示这些蛋白在特定牙髓血管周围龛的激活中发挥作用。相反,在牙髓根尖部观察到一群Notch2阳性且活跃增殖的细胞。用亲脂性DiI标记追踪这些细胞的动力学,结果显示根尖牙髓细胞向发生动态再生/修复事件的损伤部位迁移。了解病理条件下牙髓干细胞/祖细胞在其龛内的激活和调控情况,可能有助于在不久的将来实现创新性牙科治疗。