title: Local regulation of tooth mineralization by sphingomyelin phosphodiesterase 3.
abstract: Sphingomyelin phosphodiesterase 3 (Smpd3) encodes a membrane-bound enzyme that cleaves sphingomyelin to generate several bioactive metabolites. A recessive mutation called fragilitas ossium (fro) in the Smpd3 gene leads to impaired mineralization of bone and tooth extracellular matrix (ECM) in fro/fro mice. In teeth from fro/fro mice at various neonatal ages, radiography and light and electron microscopy showed delayed mantle dentin mineralization and a consequent delay in enamel formation as compared with that in control +/fro mice. These tooth abnormalities progressively improved with time. Immunohistochemistry showed expression of SMPD3 by dentin-forming odontoblasts. SMPD3 deficiency, however, did not affect the differentiation of these cells, as shown by osterix and dentin sialophosphoprotein expression. Using a transgenic mouse rescue model (fro/fro; Col1a1-Smpd3) in which Smpd3 expression is driven by a murine Col1a1 promoter fragment active in osteoblasts and odontoblasts, we demonstrate a complete correction of the tooth mineralization delays. In conclusion, analysis of these data demonstrates that Smpd3 expression in odontoblasts is required for tooth mineralization.
authors: Faculty of Dentistry, McGill University, Montreal, Quebec, Canada.
authors: Z
authors: Z
authors: Khavandgar
authors: S
authors: S
authors: Alebrahim
authors: H
authors: H
authors: Eimar
authors: F
authors: F
authors: Tamimi
authors: M D
authors: MD
authors: McKee
authors: M
authors: M
authors: Murshed
mesh_terms: D000818:Animals; D003743:Dental Enamel / Q000201:enzymology*; D003804:Dentin / Q000201:enzymology; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000201:enzymology; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009804:Odontoblasts / Q000201:enzymology; D010013:Osteogenesis Imperfecta / Q000201:enzymology* / Q000235:genetics; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics / Q000378:metabolism*; D014074:Tooth Calcification / Q000235:genetics / Q000502:physiology*
chemical_list: C491483:Smpd3 protein, mouse; D013108:Sphingomyelin Phosphodiesterase