Defective enamel and bone development in sodium-dependent citrate transporter (NaCT) Slc13a5 deficient mice

PLoS One. 2017 Apr 13;12(4):e0175465. doi: 10.1371/journal.pone.0175465. eCollection 2017.

Abstract

There has been growing recognition of the essential roles of citrate in biomechanical properties of mineralized tissues, including teeth and bone. However, the sources of citrate in these tissues have not been well defined, and the contribution of citrate to the regulation of odontogenesis and osteogenesis has not been examined. Here, tooth and bone phenotypes were examined in sodium-dependent citrate transporter (NaCT) Slc13a5 deficient C57BL/6 mice at 13 and 32 weeks of age. Slc13a5 deficiency led to defective tooth development, characterized by absence of mature enamel, formation of aberrant enamel matrix, and dysplasia and hyperplasia of the enamel organ epithelium that progressed with age. These abnormalities were associated with fragile teeth with a possible predisposition to tooth abscesses. The lack of mature enamel was consistent with amelogenesis imperfecta. Furthermore, Slc13a5 deficiency led to decreased bone mineral density and impaired bone formation in 13-week-old mice but not in older mice. The findings revealed the potentially important role of citrate and Slc13a5 in the development and function of teeth and bone.

MeSH terms

  • Animals
  • Bone Density / physiology*
  • Citric Acid / metabolism*
  • Dental Enamel / metabolism*
  • Dicarboxylic Acid Transporters / deficiency
  • Dicarboxylic Acid Transporters / metabolism*
  • Mice
  • Mice, Knockout
  • Osteogenesis / physiology*
  • Symporters / deficiency
  • Symporters / metabolism*

Substances

  • Dicarboxylic Acid Transporters
  • Slc13a5 protein, mouse
  • Symporters
  • Citric Acid

Grant support

All authors are employees of Eli Lilly & Company. Eli Lilly & Company provided financial support in the form of salaries for all authors, and research materials, but did not have any additional role in the study design, data collection and analysis, or preparation of the manuscript. Eli Lilly & Company had no role in the decision to publish, which was made by the authors, but Eli Lilly & Company was responsible for approving the authors' request to disclose the reported work to the public domain. The specific roles of all authors are articulated in the 'author contributions' section.