Role of the n-terminal peptide of amelogenin on osteoblastic differentiation of human mesenchymal stem cells

R. Olivares-Navarrete, K. Vesper, S. L. Hyzy, A. Almaguer-Flores, B. D. Boyan, Zvi Schwartz

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Porcine enamel matrix derivative (pEMD), a complex mixture of proteins and peptides including full-length amelogenin protein, splice variants, and proteolytic peptides, is used clinically with a carrier to regenerate supportive tissue around teeth. During application, pEMD self-assembles as nanospheres and precipitates as a three-dimensional matrix to facilitate cell migration and differentiation. Amelogenin, the primary constituent of pEMD, stimulates osteoblast differentiation, but it is unclear what specific roles other components of pEMD play in determining biological response. This study examined the potential of one constituent of pEMD, the N-terminal amelogenin peptide (NTAP), to promote osteoblastic differentiation of human mesenchymal stem cells (MSCs) and to elucidate possible signaling pathways involved. Effects of porcine NTAP on MSC cultures were compared to those of recombinant human amelogenin. While amelogenin induced MSC osteoblastic differentiation, a more robust osteoblastic response was seen after NTAP treatment. A phospho-kinase proteasome array measuring phosphorylation of 35 proteins indicated that protein kinase C (PKC), extracellular signal-regulated kinase 1/2 (ERK1/2), and β-catenin were highly phosphorylated by NTAP. This was confirmed by measuring PKC activity and levels of phospho-ERK1/2 and β-catenin. Both amelogenin and NTAP increased PKC, but NTAP induced higher phosho-ERK1/2 and phospho-β-catenin than amelogenin. ERK1/2 inhibition blocked both amelogenin- and NTAP-induced increases in RUNX2, ALP, OCN, COL1, and BMP2. The results demonstrate that NTAP induces osteogenic differentiation of MSCs via PKC and ERK1/2 activation and β-catenin degradation. NTAP may be an active bone regeneration component of amelogenin, and may play this role in pEMD-stimulated periodontal regeneration.

Original languageEnglish (US)
Pages (from-to)1-10
Number of pages10
JournalEuropean Cells and Materials
Volume28
StatePublished - Jul 14 2014

Fingerprint

Amelogenin
Stem cells
Mesenchymal Stromal Cells
Peptides
Enamels
Proteins
Dental Enamel
Derivatives
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Swine
Catenins
Protein Kinase C
Phosphorylation
Nanospheres
Osteoblasts
Cell Differentiation
Cell culture
Precipitates
Bone

Keywords

  • Amelogenin
  • Differentiation
  • Enamel matrix derivative
  • Local factors
  • Mesenchymal stem cells

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Bioengineering
  • Biomedical Engineering
  • Biomaterials
  • Medicine(all)

Cite this

Olivares-Navarrete, R., Vesper, K., Hyzy, S. L., Almaguer-Flores, A., Boyan, B. D., & Schwartz, Z. (2014). Role of the n-terminal peptide of amelogenin on osteoblastic differentiation of human mesenchymal stem cells. European Cells and Materials, 28, 1-10.

Role of the n-terminal peptide of amelogenin on osteoblastic differentiation of human mesenchymal stem cells. / Olivares-Navarrete, R.; Vesper, K.; Hyzy, S. L.; Almaguer-Flores, A.; Boyan, B. D.; Schwartz, Zvi.

In: European Cells and Materials, Vol. 28, 14.07.2014, p. 1-10.

Research output: Contribution to journalArticle

Olivares-Navarrete, R, Vesper, K, Hyzy, SL, Almaguer-Flores, A, Boyan, BD & Schwartz, Z 2014, 'Role of the n-terminal peptide of amelogenin on osteoblastic differentiation of human mesenchymal stem cells', European Cells and Materials, vol. 28, pp. 1-10.
Olivares-Navarrete R, Vesper K, Hyzy SL, Almaguer-Flores A, Boyan BD, Schwartz Z. Role of the n-terminal peptide of amelogenin on osteoblastic differentiation of human mesenchymal stem cells. European Cells and Materials. 2014 Jul 14;28:1-10.
Olivares-Navarrete, R. ; Vesper, K. ; Hyzy, S. L. ; Almaguer-Flores, A. ; Boyan, B. D. ; Schwartz, Zvi. / Role of the n-terminal peptide of amelogenin on osteoblastic differentiation of human mesenchymal stem cells. In: European Cells and Materials. 2014 ; Vol. 28. pp. 1-10.
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