Failure of Tooth Formation Mediated by miR-135a Overexpression via BMP Signaling

J Dent Res. 2014 Jun;93(6):571-5. doi: 10.1177/0022034514529303. Epub 2014 Mar 25.

Abstract

MicroRNAs (miRNAs) are known to regulate a variety of gene functions in many tissues and organs, but their expression and function in tooth development are not well-understood. A specific miRNA, miR-135a, was determined to be highly expressed at the bud stage. Interestingly, after the cap stage, miR-135a was expressed in the epithelium and mesenchyme but not in the inner enamel epithelium. To identify the relationship between miR-135a and its putative target genes, Bmpr-Ia and Bmpr-Ib, in early tooth development, miR-135a was ectopically overexpressed with a lentivirus. This overexpression resulted in the repression of Bmpr-Ia and Bmpr-Ib. Furthermore, miR-135a inhibited both Bmpr-Ia and Bmpr-Ib transcription. BMP2 proteins were expressed ectopically in tooth germs during the cap stage to determine the relationship between miR-135a and BMP signaling in early tooth development. When miR-135a was ectopically expressed, no tooth formation was observed after 4 wk of incubation in the kidney capsule. This study suggested that Bmp signaling, specifically Bmpr-Ia and Bmpr-Ib, regulates tooth formation via miR-135a.

Keywords: Bmp receptors; lentivirus; miRNA expression; miRNA inhibitor; microRNA; tooth development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / pharmacology
  • Bone Morphogenetic Protein Receptors, Type I / genetics*
  • Epithelium / metabolism
  • Gene Expression Regulation / genetics*
  • Genetic Vectors / genetics
  • Lentivirus / genetics
  • Male
  • Mesoderm / metabolism
  • Mice
  • Mice, Nude
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • Odontogenesis / genetics*
  • Recombinant Proteins / pharmacology
  • Signal Transduction / genetics*
  • Tooth Germ / drug effects
  • Tooth Germ / metabolism
  • Tooth Germ / transplantation
  • Transcription, Genetic / genetics
  • Transforming Growth Factor beta / pharmacology

Substances

  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • MicroRNAs
  • Mirn135 microRNA, mouse
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • recombinant human bone morphogenetic protein-2
  • Bmpr1a protein, mouse
  • Bmpr1b protein, mouse
  • Bone Morphogenetic Protein Receptors, Type I