910 Mineralization Defects of Murine Teeth and Mandible in Hereditary Hypophosphatemia

Friday, March 23, 2012: 2 p.m. - 3:15 p.m.
Presentation Type: Poster Session
A. GARCIA-GODOY1, A. KARYDIS1, V. DAVID1, A. MARTIN1, F. GARCIA-GODOY2, and L.D. QUARLES1, 1University of Tennessee, Memphis, TN, 2Bioscience Research, University of Tennessee, Memphis, TN
Objectives: The objective of this study was to investigate the incisor and mandible architecture and mineralization in mouse models of hereditary hypophosphatemia.

Dentin Matrix Protein-1 (DMP-1; non-collagenous protein) and PHEX (endopeptidase) are expressed in odontoblasts and osteoblasts and regulate extracellular matrix mineralization.  Inactivation of DMP1 and PHEX in mice results in similar bone abnormalities characterized by FGF23-mediated hypophosphatemic Rickets.  In addition, compound mutant Dmp1-/- and Hyp mice have non-additive phenotypes, suggesting a common mechanism. The relative functions of DMP1 and PHEX in teeth remains unclear.

Methods: The mandibles and incisors from 5-wk-old wild type (WT), DMP1 (Dmp-1-/-) and Hyp (Phex-1-/-) were collected and fixed in 70% ethanol (N=3/group).  High-resolution micro-computed tomography was used to evaluate tooth and bone parameters and microarchitecture. 

Results: We found that, despite similar levels of hypophosphatemia, dental abnormalities of Hyp mutant mice were more severe than in DMP1-/- mice, as evidenced by decreased dentin mineral density (Hyp:1105±8.6mgHA/cm3, DMP1:1201±15.1, WT:1257±26.81; p<0.01) ) and increased pulp chamber volume (Hyp:0.046±0.002mm3, DMP1:0.027±0.003, WT:0.015±0.001; p<0.01). 

Dentin thickness decreased (Hyp:182±2mm, DMP1:186±7, WT:239±9; p<0.01), and dentin volume (Hyp:0.296±0.01mm3, DMP1:0.2897±0.02, WT:0.263±0.008; p<0.01) and overall tooth volume (Hyp:0.397±0.01mm3, DMP1:0.374±0.018, WT:0.341±0.011; p<0.01) increased in both mutants compared with WT.  Moreover, similar decrements in mandibular bone mineral density (Hyp:789±32.8mm3, DMP1:789±22.64, WT: 1024±37.02; p<0.01) and thickness (Hyp:91.05±12.65mm3, DMP1:92.83±13, WT:172±13.08; p<0.01) were observed in both Hyp and DMP1-/- mice, consistent with prior studies showing similar defects in bone mineralization in long bones of these mutant mice. In contrast, enamel mineral density was not affected.

Conclusions: Abnormalities were observed in both mandibular incisors and mandibles in Hyp and DMP1-/- mice.  In contrast to similar defects in bone mineralization, teeth of Hyp mice exhibited more pronounced reductions in dentin mineral density and thickness compared to Dmp1-/- mice, suggesting that unlike bone, PHEX and DMP1 have distinct functions in teeth.

Keywords: Bone, Dentin, Extracellular matrix molecules, Hypophosphatemia and Mineralization