Preameloblast-Derived Factors Mediate Osteoblast Differentiation of Human Bone Marrow Mesenchymal Stem Cells by Runx2-Osterix-BSP Signaling

Tissue Eng Part A. 2016 Jan;22(1-2):93-102. doi: 10.1089/ten.TEA.2015.0272. Epub 2015 Oct 26.


Epithelial-mesenchymal interaction occurs during development of various tissues, including teeth and bone. Recently, a preameloblast-conditioned medium (PA-CM) from mouse apical bud cells (ABCs), a type of dental epithelial cell, was found to induce odontogenic differentiation of dental pulp stem cells and promote dentin formation. The aims of the present study were to investigate the effects of PA-CM on human bone marrow mesenchymal stem cells (hBMSCs) in vitro, and to investigate the bone regenerative capacity in vivo through epithelial-mesenchymal interactions of developmental osteogenesis. Coculturing with ABCs and PA-CM treatment upregulated osteoblast differentiation markers of hBMSCs compared to cells cultured alone. PA-CM accelerated mineralized nodule formation and also increased bone sialoprotein promoter activity in hBMSCs. PA-CM facilitated the migration of hBMSCs, but did not significantly influence proliferation. PA-CM promoted bone formation of hBMSCs in vivo. Radiographic and histologic findings showed that PA-CM induced the bony regeneration at calvarial defects in rat. Taken together, these data show that PA-CM enhances the migration and osteogenic differentiation of hBMSCs in vitro and induces bone formation in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ameloblasts / cytology
  • Ameloblasts / metabolism*
  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism*
  • Cell Differentiation / drug effects*
  • Core Binding Factor Alpha 1 Subunit / metabolism*
  • Culture Media, Conditioned / pharmacology*
  • Humans
  • Integrin-Binding Sialoprotein / metabolism*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*
  • Rats
  • Signal Transduction / drug effects*
  • Sp7 Transcription Factor
  • Transcription Factors / metabolism*


  • Core Binding Factor Alpha 1 Subunit
  • Culture Media, Conditioned
  • Integrin-Binding Sialoprotein
  • RUNX2 protein, human
  • Sp7 Transcription Factor
  • Sp7 protein, human
  • Transcription Factors