Prion Protein in the Developing Mouse Tooth Germ

Objective: Prion protein (PrP) is a normal cellular membrane anchored protein identified in many tissues, with prominent expression in neural tissues. A pathological conformational change in the protein structure can cause transmissible neurodegenerative disease. PrP has been recently detected in teeth, localized to odontoblasts, cementoblasts and epithelial remnants of Malassez. However, the function of PrP in tooth tissue formation is not known. The objective of this study was to determine the role of PrP in the developing dental mesenchyme.

Methods: Mandibles from newborn PrP knockout (K/O) mice and wild type (W/T) mice were isolated. Tooth tissue sections were stained with H&E and Trichrome for morphology, and von Kossa for mineralization assessment. Immunohistochemistry was used to localize PrP protein. To further study PrP function, dental mesenchymal cells were isolated from E18 mouse molar tooth germs of K/O and W/T mice. The rate of cell proliferation, and expression of collagen I, matrix extracellular phosphoglycoprotein(MEPE), and alkaline phosphatase(ALP) was compared.

Results: PrP was immunolocalized to the least mature mesenchymal cells at the root apex of the molars and in the cervical loop area of the incisor, as well as in the dental follicle. H&E and Trichrome staining showed no detectable difference in morphology of tooth tissues from W/T and K/O mice, and there was no difference in the initiation of mineralization as detected by von Kossa staining. Proliferation was significantly increased in cells from PrP K/O mice as compared to W/T. Type I collagen mRNA was reduced in PrP K/O mice compared to W/T mice, with no difference in expression of MEPE and ALP.

Conclusions: Normal PrP protein is present in early dental mesenchyme, and can function to inhibit mesenchymal cell proliferation. PrP may have a role in collagen regulation in dentin development.

This study was supported by NIDCR grants R21-DE017910 to PDB