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Imatinib inhibits p...
Imatinib inhibits proliferation of human mesenchymal stem cells and promotes early but not late osteoblast differentiation in vitro.
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Jönsson, Sofia (författare)
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Hjorth-Hansen, Henrik (författare)
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Olsson, Bob, 1969 (författare)
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visa fler...
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- Wadenvik, Hans, 1955 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
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Sundan, Anders (författare)
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Standal, Therese (författare)
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visa färre...
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(creator_code:org_t)
- 2012
- 2012
- Engelska.
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Ingår i: Journal of bone and mineral metabolism. - 1435-5604. ; 30:1, s. 119-23
- Relaterad länk:
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https://gup.ub.gu.se...
Abstract
Ämnesord
Stäng
- 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 (5μM) cultures at early time points during differentiation. On the other hand, the expression of Osterix late during differentiation was lower in imatinib-treated (5μM) 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Nyckelord
- 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
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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