The WNT inhibitor APCDD1 sustains the expression of β-catenin during the osteogenic differentiation of human dental follicle cells

Biochem Biophys Res Commun. 2015 Feb 13;457(3):314-7. doi: 10.1016/j.bbrc.2014.12.107. Epub 2015 Jan 12.

Abstract

In hair follicle cells APCDD1 inhibits the canonical WNT/β-Catenin pathway and its inactivation is associated with an autosomal dominant form of hair loss. We analyzed the role of APCDD1 for the osteogenic differentiation in dental follicle cells (DFCs) and identified a new and surprising function. Contrarily to hair follicle cells APCDD1 was crucial for the expression of β-Catenin and for the activity of the TCF/LEF reporter assay in DFCs. In addition, a depletion of APCDD1 inhibits the expression of osteogenic markers such as RUNX2 and decreased the matrix mineralization. However, similar to hair follicle cells in previous studies a control cell culture with oral squamous carcinoma cells showed that APCDD1 inhibits the expression of β-Catenin and of typical target genes of the canonical WNT/β-Catenin pathway. In conclusion, our data disclosed an unusual role of APCDD1 in DFCs during the osteogenic differentiation. APCDD1 sustains the expression and activation of β-Catenin.

Keywords: APCDD1; Dental stem cells; Osteogenic differentiation; Signaling pathway; WNT-signaling.

MeSH terms

  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Dental Sac / cytology*
  • Dental Sac / metabolism*
  • Early Growth Response Protein 1 / genetics
  • Gene Expression
  • Homeodomain Proteins / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Osteogenesis / genetics
  • Osteogenesis / physiology
  • RNA, Small Interfering / genetics
  • Transcription Factors / genetics
  • Wnt Signaling Pathway
  • beta Catenin / genetics*

Substances

  • APCDD1 protein, human
  • CTNNB1 protein, human
  • Core Binding Factor Alpha 1 Subunit
  • Distal-less homeobox proteins
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • RNA, Small Interfering
  • RUNX2 protein, human
  • Transcription Factors
  • beta Catenin