Signalings and molecular regulation of root formation and eruption of mouse incisor and molars

最有希望的牙齿组织再生方法包括复制正常发育条件和设计适当的细胞、分子因子和支架组合以促进组织再生。Hertwig上皮根鞘(HERS)的发育和牙骨质的形成是牙根形成和萌发的关键步骤。因此，我们对HERS细胞在小鼠磨牙根形成过程中的发育进行了系统的研究。她和根之间的这种不成比例的生长速度可能解释了她的窗口期。免疫组织化学结果显示，HERS可能通过分泌成纤维细胞生长因子来促进成牙本质细胞的分化，其增殖和构筑受多种生长因子、EGF、IGF和5-羟色胺的调节。细胞增殖分析表明，HERS细胞在生根初期表现出显著的增殖活性，而HERS的增殖速度与促进根生长的结缔组织细胞的增殖速度不匹配。为了跟踪HERS细胞在发育中的牙根表面的去向和分布，我们用抗角蛋白抗体标记上皮细胞，然后对出生后发育中的小鼠下颌第一磨牙进行了抗角蛋白标记的连续切片的三维重建。3D观察和组织形态计量学分析支持HERS细胞的四种可能的命运：细胞凋亡，整合到推进的细胞牙骨质前沿，从根面迁移到牙周膜，以及上皮-间充质转化。关于HERS细胞的迁移能力，证实了少数HERS细胞从牙根表面迁移到形成Malassez支架，这在牙周韧带间隙的调节和维持中起着重要作用。

Most promising approaches toward dental tissue regeneration include replication of normal developmental conditions and design of appropriate combinations of cells, molecular factors, and scaffolds to promote tissue regrowth. Development of Hertwig's epithelial root sheath (HERS) and cementogenesis are crucial steps in root formation and eruption. Thus we performed a systematic study of the development of HERS cells throughout mouse molar root formation. This disproportionate growth rate between HERS and root likely explains the fenestration of HERS. Immunohistochemistry showed that HERS may stimulate odontoblast differentiation through FGF secretion and that proliferation and architecture of HERS are under regulation of several growth factors, e/g., EGF, IGF and serotonin. Cell proliferation assays revealed that HERS cells during initial root formation exhibit significant proliferation activities, whereas HERS proliferation rates do not match the proliferation rates of connective tissue cells contributing to root growth. In order to follow the fate and distribution of HERS cells along the developing root surface, we marked epithelial cells with ant-keratin antibodies and then conducted 3D reconstructions of anti-keratin labeled serial sections of postnatal developing mouse first mandibular molars. 3D observations and histomorphometric analysis supported four possible fates of HERS cells: apoptosis, incorporation into the advancing cellular cementum front, migration away from the root surface into the periodontal ligament, and epithelial-mesenchymal transformation. Regarding the migratory capacity of HERS cells, it was validated that a few HERS cells migrate away from the root surface to form the rests of Malassez, which play significant roles in the regulation and maintenance of the periodontal ligament space.