Multiple effects of the cellular prion protein on tooth development

Abstract

The role of the prion protein (PrP) in transmissible spongiform encephalopathies has been the focus of intense investigation. However, less is known about the physiological function of normal cellular PrP (PrP C ). In adult human teeth, PrP C has been identified in odontoblasts, cementoblasts and epithelial remnants of Malassez. In this study, we have localized PrP C in developing human and mouse teeth, and investigated the function of PrP using a PrP-knockout (Prnp 0/0 ) mouse model. PrP C was detected in developing human and mouse ameloblasts and odontoblasts. In vitro, undifferentiated dental mesenchymal cells from embryonic day 18 (E18) Prnp 0/0 mouse molars proliferated much more rapidly compared to age-matched, wild-type (wt) mouse molar dental mesenchymal cells. Histochemistry and immunohistochemical analyses showed a subtle but measurable phenotype, with the absence of PrP resulting in earlier initiation of both dentin and enamel formation. Consistent with this finding, laser microdissected odontoblasts from newborn Prnp 0/0 mouse incisors had a reduced proliferation rate, as measured by the expression of proliferating cell nuclear antigen (PCNA), and increased type 1 collagen mRNA expression. Dentin microhardness of the fully erupted molars was reduced and incisal enamel mineralization was delayed in Prnp 0/0 compared to age-matched wt mouse teeth. Taken together, these results suggest that PrP C affects multiple processes involved in tooth formation, through regulating the differentiation of ameloblasts and odontoblasts.

Comparative Gene Expression Analysis of the Human Periodontal Ligament in Deciduous and Permanent Teeth

“…The following TaqMan gene expression assay primers (Applied Biosystems) were used: chemokine (C-C motif) ligand 21 ( CCL21 ), laminin subunit γ-2 ( LAMC2 ), insulin-like growth factor 2 mRNA-binding protein 1 ( IGF2BP1 ), interleukin (IL)-6 ( IL6 ), ADAM metalloproteinase with thrombospondin motifs-like 3 ( ADAMTSL3 ), and leucine-rich repeat transmembrane neuronal protein 1 ( LRRTM1 ). 18S rRNA which is known to be a reliable housekeeping gene, was used as an internal control [21]–[23]. ABI 7300 SDS 1.3.1 software (Applied Biosystems) recorded the fluorescence intensity of the reporter and quencher dyes; the results are plotted versus time, quantified as the cycle number.…”

Expression of antimicrobial peptides and E‐cadherin in periapical lesions

“…Enamel is the only mineralized epithelial‐derived tissue in teeth, and it is said that the hard acellular mineral enamel structure is formed to protect dentin and the pulp complex []. Destruction of the dental hard tissue wall resulting from caries, trauma‐induced fractures, and cracks are the most frequent portals of pulpal infection [].…”

Estimated Time of Biomineralization in Developing Rat Incisors

“…The dental epithelial precursor cells located in the cervical loop migrate to the basal layer around the outside of the loop. The basal epithelial cells polarize and elongate to become pre-ameloblasts, and then differentiate into secretory ameloblasts, which secrete enamel matrix proteins and attract minerals to initiate enamel biomineralization [20]. The developmental stages of the rat lower incisor could be divided into four stages in this study according to Pingping's method [21]: (1) presecretory odontoblast: before secretion of dentin matrix, (2) presecretory ameloblast: Secretion of dentin matrix, (3) secretory ameloblast:…”

“…computerized tomography (micro-CT), measuring from the posterior wall of cervical loop to the following four radiographically observed stages according to Yan's method[20]:(1) initiation of dentin calcification, (2) initiation of enamel matrix secretion, (3) endpoint of enamel secretion, and (4) starting point of almost complete calcified enamel. The hard tissues of the desired teeth were reconstructed in three dimensions from the radiologic findings(Fig.…”