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Retinoic acid inhibits the growth of bone marrow mesenchymal stem cells and induces p27Kip1 and p16INK4A up-regulation

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Abstract

The importance of bone marrow mesenchymal stem cells in hemopoiesis has been definitely demonstrated. Thus, their impairment might cause profound alteration on production and maturation of blood cells. In the present paper, we investigated, for the first time, the effect of retinoic acid, an important antileukemic molecule, on the proliferation of primary cultures of human bone marrow mesenchymal stem cells. We demonstrated that retinoic acid, at a pharmacological concentration, hampers strongly the growth of the cells, without inducing osteoblastic differentiation. The analysis of cell division cycle machinery showed that the antiproliferative effect is associated with (i) the up-regulation of two cyclin-dependent kinase inhibitors, namely p27Kip1 and p16INK4A, and (ii) the down-regulation of cyclin-dependent kinase 2 activity and pRB phosphorylation. The reported findings represent novel insights into the antileukemic effects of the drug and contribute in clarifying the molecular mechanism of its pharmacological activity.

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Authors and Affiliations

  1. Department of Biochemistry and Biophysics, ‘F. Cedrangolo’, Second University of Naples, Via De Grecchio 7, 80138, Naples, Italy

    Adriana Oliva, Adriana Borriello, Stefania Zeppetelli, Angelo Di Feo, Pilade Cortellazzi, Vega Ventriglia, Maria Criscuolo, Vincenzo Zappia & Fulvio Della Ragione

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  1. Adriana Oliva
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  2. Adriana Borriello
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  3. Stefania Zeppetelli
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  4. Angelo Di Feo
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  5. Pilade Cortellazzi
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  6. Vega Ventriglia
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  7. Maria Criscuolo
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  8. Vincenzo Zappia
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  9. Fulvio Della Ragione
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Oliva, A., Borriello, A., Zeppetelli, S. et al. Retinoic acid inhibits the growth of bone marrow mesenchymal stem cells and induces p27Kip1 and p16INK4A up-regulation. Mol Cell Biochem 247, 55–60 (2003). https://doi.org/10.1023/A:1024192719178

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  • DOI: https://doi.org/10.1023/A:1024192719178

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