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.
