Osteopetrosis, osteopetrorickets and hypophosphatemic rickets differentially affect dentin and enamel mineralization

Osteopetrosis (OP) is an inherited disorder of defective bone resorption, which can be accompanied by impaired skeletal mineralization, a phenotype termed osteopetrorickets (OPR). Since individuals with dysfunctional osteoclasts often develop osteomyelitis of the jaw, we have analyzed, if dentin and enamel mineralization are differentially affected in OP and OPR. Therefore, we have applied non-decalcified histology and quantitative backscattered electron imaging (qBEI) to compare the dental phenotypes of Src−/−, oc/oc and Hyp−/0 mice, which serve as models for OP, OPR and hypophosphatemic rickets, respectively. While both, Src−/− and oc/oc mice, were characterized by defects of molar root formation, only oc/oc mice displayed a severe defect of dentin mineralization, similar to Hyp−/0 mice. Most importantly, while enamel thickness was not affected in either mouse model, the calcium content within the enamel phase was significantly reduced in oc/oc, but not in Src−/− or Hyp−/0 mice. Taken together, these data demonstrate that dentin and enamel mineralization are differentially affected in Src−/− and oc/oc mice. Moreover, since defects of dental mineralization may trigger premature tooth decay and thereby osteomyelitis of the jaw, they further underscore the importance of discriminating between OP and OPR in the respective individuals.

► Molar root formation is severely impaired in mouse models of osteopetrosis (Src−/−) and osteopetrorickets (oc/oc).
► Dentin mineralization in oc/oc mice is similarly disturbed as in Hyp−/0 mice, a model of hypophosphatemic rickets.
► Only oc/oc mice, but not Src−/− and Hyp−/0 mice, display enamel hypomineralization.