Insights into dental mineralization from three heritable mineralization disorders.

Abstract

Teeth are comprised of three unique mineralized tissues, enamel, dentin, and cementum, that are susceptible to developmental defects similar to those affecting bone. X-linked hypophosphatemia (XLH), caused by PHEX mutations, leads to increased fibroblast growth factor 23 (FGF23)-driven hypophosphatemia and local extracellular matrix disturbances. Hypophosphatasia (HPP), caused by ALPL mutations, results in increased levels of inorganic pyrophosphate (PPi), a mineralization inhibitor. Generalized arterial calcification in infancy (GACI), caused by ENPP1 mutations, results in vascular calcification due to decreased PPi, later compounded by FGF23-driven hypophosphatemia. In this perspective, we compare and contrast dental defects in primary teeth associated with XLH, HPP, and GACI, briefly reviewing genetic and biochemical features of these disorders and findings of clinical and preclinical studies to date, including some of our own recent observations. The distinct dental defects associated with the three heritable mineralization disorders reflect unique processes of the respective dental hard tissues, revealing insights into their development and clues about pathological mechanisms underlying such disorders.

• Authors: Michael B Chavez, Kaitrin Kramer, Emily Y Chu, Vivek Thumbigere-Math, Brian L Foster
• Journal: Journal of structural biology (J Struct Biol) Vol. 212 Issue 1 Pg. 107597 (10 01 2020) ISSN: 1095-8657 [Electronic] United States
• PMID: 32758526 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Published by Elsevier Inc.

Chemical References

• FGF23 protein, human
• Fibroblast Growth Factors
• Fibroblast Growth Factor-23
• Alkaline Phosphatase

Topics

• Alkaline Phosphatase (metabolism)
• Animals
• Calcification, Physiologic (physiology)
• Extracellular Matrix (metabolism, physiology)
• Familial Hypophosphatemic Rickets (metabolism, physiopathology)
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors (metabolism)
• Humans
• Hypophosphatasia (metabolism, physiopathology)
• Tooth (metabolism, physiology)
• Vascular Calcification (metabolism, physiopathology)