Multiple effects of the cellular prion protein on tooth development
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Yan Zhang [1] ; Seong- Oh Kim ; Sibylle Opsahl- Vital ; Sunita p. Ho ; Jean- Baptiste Souron ; Charles W. Kim ; Kurt Giles ; Pamela K. Den Besten
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[1] University of California, San Francisco
University of California, San Francisco
Estados Unidos
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- Localización: International journal of developmental biology, ISSN 0214-6282, Vol. 55, Nº. 10-12, 2011, págs. 953-960
- Idioma: inglés
- Texto completo no disponible (Saber más ...)
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Resumen
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 (PrPC). In adult human teeth, PrPC has been identified in odontoblasts, cementoblasts and epithelial remnants of Malassez. In this study, we have localized PrPC in developing human and mouse teeth, and investigated the function of PrP using a PrP-knockout (Prnp0/0 ) mouse model. PrPC was detected in developing human and mouse ameloblasts and odontoblasts. In vitro, undifferentiated dental mesenchymal cells from embryonic day 18 (E18) Prnp0/0 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 Prnp0/0 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 Prnp0/0 compared to age-matched wt mouse teeth. Taken together, these results suggest that PrPC affects multiple processes involved in tooth formation, through regulating the differentiation of ameloblasts and odontoblasts.
