Frontiers Between Science and Clinic in Odontology Volume Title: Phosphorylated Extracellular Matrix Proteins of Bone and Dentin

Phospholipids: Implication in Bone and Dentin Mineralization

Author(s): Michel Goldberg, Arnaud Marchadier, Anne Negre-Salvayre, Robert Salvayre, Yassine Harichane, Sasha Dimitrova-Nakov, Catherine Vidal and Agnès Kamoun-Goldrat

Pp: 401-421 (21)

DOI: 10.2174/978160805465711202010401

* (Excluding Mailing and Handling)


As cellular components, phospholipids (PLs) are signalling molecules implicated in the regulation of stress-induced cellular responses, cell differentiation, proliferation, and cell death. The chemical comparison between demineralized and undemineralized tissues provides evidences that a specific group of PLs is present as extracellular matrix (ECM) component, and related to the mineralization process. Matrix vesicles, extensively studied in the growth plate of cartilage, are also implicated in the initial stages of bone and dentin mineralization. They play a key role in the formation of calcium-phosphate-lipoprotein complexes (CPLX) found in most mineralizing tissues. Radioautographic investigations suggest the transfer of PLs originating in the blood serum. Using an intercellular pathway they migrate directly toward the mineralization front in dentin. Genetic and pharmacological PLs alterations lead to lysosomal storage diseases, which have apparently little effects on dentin and bone mineralization. As another model to investigate, the fro-/- mice clarify the role(s) of PLs in mineralization. Positional cloning of the mutation was found to be a deletion in Smpd3, the gene encoding sphingomyelin phosphodiesterase 3 (neutral sphingomyelinase-2). The mutation was found on mouse chromosome 8. The deletion of the intron 8 - exon 9 is producing a non-functional mutant protein. As a consequence of the mutation, the fro -/- mice display defective mineralization, i.e. a non-collagenous form of osteogenesis imperfecta associated with dentin dysplasia/dentinogenesis imperfecta. This suggests that enzymatic cleavage of ECM PLs may be a pre-requisite for dentin and bone mineralization.

Keywords: Phospholipids, matrix vesicles, cartilage, calcium-phosphatelipoprotein complexes, lysosomal storage diseases, dentin mineralization, bone mineralization, sphingomyelins phosphodiesterase 3, fro-/- mice, osteogenesis imperfecta, dentinogenesis imperfecta.

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