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The effect of PKC activation and inhibition on osteogenic differentiation of human mesenchymal stem cells
Author(s) -
Liu Jun,
Someren Eugene,
Mentink Anouk,
Licht Ruud,
Dechering Koen,
van Blitterswijk Clemens,
de Boer Jan
Publication year - 2010
Publication title -
journal of tissue engineering and regenerative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.835
H-Index - 72
eISSN - 1932-7005
pISSN - 1932-6254
DOI - 10.1002/term.242
Subject(s) - mesenchymal stem cell , protein kinase c , chemistry , microbiology and biotechnology , alkaline phosphatase , cellular differentiation , phorbol , stem cell , kinase , biology , biochemistry , enzyme , gene
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. Copyright © 2009 John Wiley & Sons, Ltd.