Genetic reduction or deletion of osteopontin in osteomalacic Hyp mice fails to ameliorate dentoalveolar defects.

X-linked hypophosphatemia (XLH) is caused by inactivating mutations in PHEX, leading to disturbed mineral metabolism, rickets, and osteomalacia. Dentoalveolar defects affecting dentin, cementum, and alveolar bone, contribute to dental abscesses and periodontal breakdown. Limited efficacy of current therapies for ameliorating XLH-associated dentoalveolar effects suggests mechanisms of disease that remain unchecked. Increased production and abnormal distribution of osteopontin (OPN) is thought to contribute to XLH-associated mineralization defects. Osteopontin is a secreted phosphoprotein and mineralization inhibitor, and a substrate of PHEX. To investigate the potential role of OPN in the pathology of XLH-associated dentoalveolar defects, a genetic approach was used to ablate or diminish Spp1/OPN in the Hyp mouse model of XLH. One or both Spp1 alleles in Hyp mice were deleted and tissues were analyzed at 60 d postnatally (dpn). Micro-CT showed no differences in volumes or densities of dentin and alveolar bone in Hyp mice lacking one or both Spp1 alleles, as compared to control Hyp mice. Histological assessment showed no improvements in cementum or periodontal ligament attachment, and dynamic mechanical analysis revealed no normalization of periodontal mechanical properties. While OPN may play a role in regulating dentoalveolar mineralization, diminishing OPN alone was not sufficient to substantially ameliorate XLH-associated defects.