Local regulation of tooth mineralization by sphingomyelin phosphodiesterase 3

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. © 2013 international & american associations for dental research.