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Imatinib inhibits proliferation of human mesenchymal stem cells and promotes early but not late osteoblast differentiation in vitro.
J Bone Miner Metab 2012; 30(1):119-23JB

Abstract

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.

Authors+Show Affiliations

Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway. sofia.jonsson@vgregion.seNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21993629

Citation

Jönsson, Sofia, et al. "Imatinib Inhibits Proliferation of Human Mesenchymal Stem Cells and Promotes Early but Not Late Osteoblast Differentiation in Vitro." Journal of Bone and Mineral Metabolism, vol. 30, no. 1, 2012, pp. 119-23.
Jönsson S, Hjorth-Hansen H, Olsson B, et al. Imatinib inhibits proliferation of human mesenchymal stem cells and promotes early but not late osteoblast differentiation in vitro. J Bone Miner Metab. 2012;30(1):119-23.
Jönsson, S., Hjorth-Hansen, H., Olsson, B., Wadenvik, H., Sundan, A., & Standal, T. (2012). Imatinib inhibits proliferation of human mesenchymal stem cells and promotes early but not late osteoblast differentiation in vitro. Journal of Bone and Mineral Metabolism, 30(1), pp. 119-23. doi:10.1007/s00774-011-0323-3.
Jönsson S, et al. Imatinib Inhibits Proliferation of Human Mesenchymal Stem Cells and Promotes Early but Not Late Osteoblast Differentiation in Vitro. J Bone Miner Metab. 2012;30(1):119-23. PubMed PMID: 21993629.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Imatinib inhibits proliferation of human mesenchymal stem cells and promotes early but not late osteoblast differentiation in vitro. AU - Jönsson,Sofia, AU - Hjorth-Hansen,Henrik, AU - Olsson,Bob, AU - Wadenvik,Hans, AU - Sundan,Anders, AU - Standal,Therese, Y1 - 2011/10/14/ PY - 2011/05/04/received PY - 2011/09/04/accepted PY - 2011/10/14/entrez PY - 2011/10/14/pubmed PY - 2012/5/15/medline SP - 119 EP - 23 JF - Journal of bone and mineral metabolism JO - J. Bone Miner. Metab. VL - 30 IS - 1 N2 - 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. SN - 1435-5604 UR - https://www.unboundmedicine.com/medline/citation/21993629/abstract/ L2 - https://dx.doi.org/10.1007/s00774-011-0323-3 DB - PRIME DP - Unbound Medicine ER -