Int. J. Dev. Biol. 55: 953 - 960 (2011)

https://doi.org/10.1387/ijdb.113348yz

Vol 55, Issue 10-11-12

Multiple effects of the cellular prion protein on tooth development

Original Article | Published: 29 September 2011

Yan Zhang¹, Seong-Oh Kim^1,2, Sibylle Opsahl-Vital^1,3, Sunita P. Ho⁴, Jean-Baptiste Souron³, Charles Kim¹, Kurt Giles^5,6 and Pamela K. Den Besten*^,1

¹Department of Orofacial Sciences, University of California San Francisco, USA, ²Department of Pediatric Dentistry, Oral Science Research Center, College of Dentistry, Yonsei University, Seoul, Korea, ³University Paris Descartes, EA2496, AP-HP, France, ⁴Division of Biomaterials and Bioengineering, Department of Preventive and Restorative Dental Sciences, ⁵Institute for Neurodegenerative Diseases and ⁶Department of Neurology, University of California San Francisco, USA

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.

Keywords

tooth development, prion protein, ameloblast, odontoblast