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

牙齿组织再生最有前途的方法包括复制正常的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）的发育和牙骨质形成是牙根形成和萌出的关键步骤。因此，我们进行了系统的研究，在整个小鼠磨牙牙根形成的HERS细胞的发展。HERS和根之间的这种不成比例的生长速率可能解释了HERS的开窗。免疫组化显示HERS可能通过FGF分泌刺激成牙本质细胞分化，并且HERS的增殖和结构受几种生长因子的调节，EGF、IGF和血清素细胞增殖试验表明，HERS细胞在最初的根形成表现出显着的增殖活性，而HERS增殖率不匹配的结缔组织细胞的增殖率有助于根的生长。为了跟踪HERS细胞沿着发育中的牙根面的命运和分布，我们用抗角蛋白抗体标记上皮细胞，然后对抗角蛋白标记的出生后发育中的小鼠下颌第一磨牙的连续切片进行3D重建。三维观察和组织形态学分析支持HERS细胞的四种可能的命运：细胞凋亡，掺入到前进的细胞牙骨质前，迁移远离牙根表面进入牙周膜，上皮间充质转化。关于HERS细胞的迁移能力，已经证实，少数HERS细胞迁移离开牙根表面形成Malassez的剩余部分，其在牙周膜间隙的调节和维持中起重要作用。

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.