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Imatinib inhibits proliferation of human mesenchymal stem cells and promotes early but not late osteoblast differentiation in vitro.

Artikel i vetenskaplig tidskrift
Författare Sofia Jönsson
Henrik Hjorth-Hansen
Bob Olsson
Hans Wadenvik
Anders Sundan
Therese Standal
Publicerad i Journal of bone and mineral metabolism
Volym 30
Nummer/häfte 1
Sidor 119-23
ISSN 1435-5604
Publiceringsår 2012
Publicerad vid Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition
Sidor 119-23
Språk en
Ämnesord Cell Differentiation, drug effects, Cell Line, Cell Proliferation, drug effects, Humans, Mesenchymal Stromal Cells, cytology, drug effects, Osteoblasts, cytology, drug effects, Piperazines, pharmacology, Pyrimidines, pharmacology
Ämneskategorier Hematologi

Sammanfattning

Altered bone metabolism has been reported in patients with chronic myeloid leukemia treated with the tyrosine kinase inhibitor imatinib. Several studies have shown that imatinib inhibits the differentiation and activity of osteoclasts in vitro, whereas the effects of imatinib on osteoblast differentiation are less clear. In this study osteoblast differentiation was induced in human mesenchymal stem cells (hMSCs) by treatment with bone morphogenetic protein 2 in vitro. Imatinib inhibited proliferation of hMSCs in a dose-dependent manner. Even though imatinib promoted early osteoblast differentiation assessed by alkaline phosphate activity, mineralization measured by Alizarin Red staining (ARS) was reduced by imatinib. Moreover, the inhibitory effect of imatinib on mineralization was most prominent at low concentrations of imatinib. When we measured the relative mRNA expression levels of Runx2, we found that Runx2 expression was higher in imatinib-treated (5 μM) cultures at early time points during differentiation. On the other hand, the expression of Osterix late during differentiation was lower in imatinib-treated (5 μM) cultures, corresponding to the ARS results. Thus, the effect of imatinib on osteoblast differentiation is not only dependent on the drug concentration, but indeed also on the maturation stage of the cells. This finding might partly explain why previous studies on the effects of imatinib osteoblast differentiation have shown different results.

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