The effect of PKC activation and inhibition on osteogenic differentiation of human mesenchymal stem cells

Jun Liu, Eugene Someren, Anouk Mentink, Ruud Licht, Koen Dechering, Clemens Van Blitterswijk, Jan De Boer

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)

Abstract

Human mesenchymal stem cells (hMSCs) are being considered for several areas of clinical therapy, due to their multipotent nature. For instance, osteogenic hMSCs are applied in bone tissue engineering, but current differentiation protocols need further optimization before they can be clinically applied. Protein kinase C (PKC) family members have been implicated in bone metabolism, which prompted us to use a pharmaceutical approach to manipulate PKC signalling in hMSCs. Inhibition of PKC resulted in a dose-dependent inhibition of dexamethasone-induced osteogenic differentiation. Surprisingly, PKC activation using phorbol 12-myristate 13-acetate (PMA) also resulted in inhibition of osteogenesis, although we observed that inhibition was more pronounced at low than at high concentrations of PMA. Furthermore, we observed that inhibition of PKCδ blocked alkaline phosphatase (ALP, an early marker of osteogenic differentiation) expression, whereas inhibition of the conventional PKC subfamily and PKCμ using Gö6976 resulted in an induction of ALP activity, collagen (I) expression and mineralization. In conclusion, inhibition of the conventional PKCs/PKCμ and activation of PKCδ could further benefit osteogenic differentiation of hMSCs in vitro and in vivo, which is currently under investigation.

Original languageEnglish
Pages (from-to)329-339
Number of pages11
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume4
Issue number5
DOIs
Publication statusPublished - 1 Jul 2010
Externally publishedYes

Keywords

  • Bone tissue engineering
  • Human mesenchymal stem cells
  • Protein kinase C

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