Hertwig’s Epithelial Root Sheath Fate during Initial Cellular Cementogenesis in Rat Molars

Abstract

To elucidate the fate of the epithelial root sheath during initial cellular cementogenesis, we examined developing maxillary first molars of rats by immunohistochemistry for keratin, vimentin, and tissue non-specific alkaline phosphatase (TNALP) and by TdT-mediated dUTP nick end labeling (TUNEL). The advancing root end was divided into three sections, which follow three distinct stages of initial cellular cementogenesis: section 1, where the epithelial sheath is intact; section 2, where the epithelial sheath becomes fragmented; and section 3, where initial cellular cementogenesis begins. After fragmentation of the epithelial sheath, many keratin-positive epithelial sheath cells were embedded in the rapidly growing cellular cementum. A few unembedded epithelial cells located on the cementum surface. Dental follicle cells, precementoblasts, and cementoblasts showed immunoreactivity for vimentin and TNALP. In all three sections, there were virtually no cells possessing double immunoreactivity for vimentin-keratin or TNALP-keratin and only embedded epithelial cells showed TUNEL reactivity. Taken together, these findings suggest that: (1) epithelial sheath cells divide into two groups; one group is embedded in the cementum and thereafter dies by apoptosis, and the other survives on the cementum surface as epithelial cell rests of Malassez; and (2) epithelial sheath cells do not undergo epithelial-mesenchymal transition during initial cellular cementogenesis.

Multiple essential MT1-MMP functions in tooth root formation, dentinogenesis, and tooth eruption

“…Based on structural alterations in HERS of MT1-MMP −/− mice, we analyzed cellular processes and signaling pathways previously suggested to be important for HERS function and root formation including proliferation and apoptosis [15-17], Wnt signaling [18], and NFIC expression [19]. PCNA immunohistochemistry indicated similar proliferation potential in 14 dpn WT and MT1-MMP −/− mouse molars, and similar numbers of TUNEL-positive apoptotic cells in the region of WT and MT1-MMP −/− HERS (Supplementary Figure 3A-D).…”

Histology of human cementum: Its structure, function, and development

“…Therefore, in the in vivo studies epithelial cell rests and embedded epithelial cells were probably misidentified as cementoblasts and cementocytes, respectively. Findings supportive of the classical mesenchymal hypothesis have also accumulated in in vivo studies using mouse and rat teeth [56] , [58] , [59] , [69] , [70] , [71] . In these studies any epithelial sheath-derived cells did not express mesenchymal or cementoblast characteristics, e.g.…”

“…This hypothesis will be referred to as an alternative epithelial hypothesis [45] . The alternative epithelial hypothesis has now almost surpassed the classical mesenchymal hypothesis, because the alternative epithelial hypothesis can explain why epithelial sheath cells decrease in number during epithelial sheath disintegration [56] , [57] , [58] , [59] . EMT is a normal phenomenon in embryos in several developing organs, e.g.…”

“…The epithelial cells decrease in number during epithelial sheath disintegration when observed in histological sections [56] , [57] , [58] , [59] . If EMT does not occur, how can the cell number reduction be explained?…”

Differentiation of Apical Bud Cells in a Newly Developed Apical Bud Transplantation Model Using GFP Transgenic Mice as Donor

“…The secondary purpose of this experiment is to investigate the so far unproven hypothesis that cementoblasts in the periodontal ligament are derived from epithelial precursor cells [ 11 – 15 ]. Some researches failed to show the evidence of the epithelial root sheath (ERS) to undergo epithelial-mesenchymal transition (EMT) during initial cellular cementogenesis [ 16 , 17 ]. Whether the ERS is influencing the residual mesenchymal cells to differentiate into cementoblasts, or whether sheath cells themselves can become cementoblasts through EMT is still unknown.…”