Effects of Sphingomyelin Phosphodiesterase 3 Deletion on Osteogenesis/Dentinogenesis Imperfecta

Objectives: Our aim was to further characterize the phenotype of the teeth in this animal model.

Methods: Histochemical investigations were carried out on fro-/fro- and WT newborn mice. Von Kossa staining, immunolocalisation of CS/DS GAGs, decorin, biglycan, dentin sialoprotein, MEPE, osteopontin, ostonectin, amelogenin and MMP-2,-9, -3 were carried out. We also investigated the proliferative cell nuclear antigen (PCNA) and apoptosis with the TUNEL method.

Results: Von Kossa staining revealed a reduced mineralization of alveolar bone and dentin in the fro-/fro- as compared with WT. CS/DS were increased, but no difference was detected for decorin and biglycan. DSP was decreased, whereas MEPE was increased. Immunolabelling did not show reveal any difference for MMP-2, -9 and -3. PCNA staining was dramatically reduced in the fro-/fro- mouse. This was indicative of proliferation impairment, whereas no difference in apoptosis was noted with the TUNEL technique. The lack of cell proliferation clearly accounts for the reduced growth differences in the mutant teeth.

Conclusion: As an intracellular enzyme, Smpd3 is involved both in cell proliferation and apoptosis. The effect on proliferation may be an indirect cause of the alterations seen in the fro/fro mouse. As an extracellular enzyme, Smpd3 may be directly involved in matrix sphingomyelin catabolism, a lipid found in dental tissues both as membrane- associated and mineral-associated matrix component. These data evidence that lipids are actually implicated in bone and dentin mineralization.