The specific role of FAM20C in dentinogenesis

J Dent Res. 2015 Feb;94(2):330-6. doi: 10.1177/0022034514563334. Epub 2014 Dec 16.

Abstract

FAM20C is an evolutionarily reserved molecule highly expressed in mineralized tissues. Previously we demonstrated that Sox2-Cre;Fam20C(fl/fl) mice, in which Fam20C was ubiquitously inactivated, had dentin and enamel defects as well as hypophosphatemic rickets. We also showed that K14-Cre;Fam20C(fl/fl) mice, in which Fam20C was specifically inactivated in the epithelium, had enamel defects but lacked hypophosphatemia and defects in the bone and dentin. These results indicated that the enamel defects in the Sox2-Cre;Fam20C(fl/fl) mice were independent of dentin defects and hypophosphatemia. To determine if the dentin defects in the Sox2-Cre;Fam20C(fl/fl) mice were associated with the enamel defects and hypophosphatemia, we crossed Fam20C(fl/fl) mice with Wnt1-Cre and Osr2-Cre transgenic mice to inactivate Fam20C in the craniofacial mesenchymal cells that form dentin and alveolar bone. The resulting Wnt1-Cre;Fam20C(fl/fl) and Osr2-Cre;Fam20C(fl/fl) mice showed remarkable dentin and alveolar bone defects, while their enamel did not show apparent defects. The serum FGF23 levels in these mice were higher than normal but lower than those in the Sox2-Cre;Fam20C(fl/fl) mice; they developed a mild type of hypophosphatemia that did not cause major defects in long bones. These results indicate that the dentin defects in the Sox2-Cre;Fam20C(fl/fl) mice were independent of the enamel defects.

Keywords: FGF23; bone; dentin; enamel; hypophosphatemia; neural crest cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alveolar Process / abnormalities
  • Animals
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / physiology*
  • Dental Enamel / anatomy & histology
  • Dentin / abnormalities
  • Dentinogenesis / genetics
  • Dentinogenesis / physiology*
  • Extracellular Matrix Proteins / analysis
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / physiology*
  • Fibroblast Growth Factor-23
  • Fibroblast Growth Factors / blood
  • Gene Silencing
  • Hypophosphatemia / etiology
  • Integrases / genetics
  • Mandible / chemistry
  • Mandible / pathology
  • Mesenchymal Stem Cells / cytology
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Osteogenesis / genetics
  • Osteogenesis / physiology
  • Phosphoproteins / analysis
  • SOXB1 Transcription Factors / genetics
  • Sialoglycoproteins / analysis
  • Tibia / chemistry
  • Tibia / pathology
  • Transcription Factors / genetics
  • Wnt1 Protein / genetics
  • Zinc Fingers / genetics

Substances

  • Calcium-Binding Proteins
  • Dmp1 protein, mouse
  • Extracellular Matrix Proteins
  • FAM20C protein, mouse
  • Fgf23 protein, mouse
  • Osr2 protein, mouse
  • Phosphoproteins
  • SOXB1 Transcription Factors
  • Sialoglycoproteins
  • Sox2 protein, mouse
  • Transcription Factors
  • Wnt1 Protein
  • Wnt1 protein, mouse
  • dentin sialophosphoprotein
  • Fibroblast Growth Factors
  • Fibroblast Growth Factor-23
  • Cre recombinase
  • Integrases