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

J. Liu, Eugene Someren, Anouk Mentink, R. Licht, Koen Dechering, Clemens van Blitterswijk, Jan de Boer

Research output: Contribution to journalArticleAcademic

8 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 languageUndefined
Pages (from-to)329-339
JournalJournal of tissue engineering and regenerative medicine
Volume4
Issue number5
DOIs
Publication statusPublished - 2010

Keywords

  • IR-72713
  • Human mesenchymal stem cells
  • Bone tissue engineering
  • protein kinase C

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