Dentin alteration of deciduous teeth in human hypophosphatemic rickets.

Familial hypophosphatemic rickets is in most cases transmitted as an X-linked dominant trait and results from mutation of the PHEX gene, predominantly expressed in osteoblast and odontoblast. Patients have been reported to display important dentin defects, and therefore, we explored the dentin structure, composition, and distribution of extracellular matrix (ECM) molecules in hypophosphatemic human deciduous teeth. Compared to age-matched controls, the dentin from hypophosphatemic patients exhibited major differences: presence of large interglobular spaces resulting from the lack of fusion of calcospherites in the circumpulpal dentin; defective mineralization in the interglobular spaces contrasting with normal Ca-P levels in the calcospherites on X-ray microanalysis; abnormal presence of low-molecular weight protein complexes recognized on Western blots by antibodies against matrix extracellular phosphoglycoprotein (MEPE), dentin sialoprotein, osteopontin, and reduced osteocalcin (OC) level; and accumulation in the interglobular spaces of immunolabeling with antibodies against DSP, dentin matrix protein, bone sialoprotein, MEPE and OC, while chondroitin/dermatan sulfate glycosaminoglycans were exclusively located inside calcospherites. Alterations of the post-translational processing or partial degradation of some ECM appear as key factors in the formation of the defective hypophosphatemic dentin.