Imatinib mesylate and nilotinib decrease synthesis of bone matrix in vitro

  • Authors:
    • Lysann Michaela Kroschwald
    • Josephine Tabea Tauer
    • Sonja Ingrid Kroschwald
    • Meinolf Suttorp
    • Anne Wiedenfeld
    • Stefan Beissert
    • Andrea Bauer
    • Martina Rauner
  • View Affiliations

  • Published online on: June 21, 2019     https://doi.org/10.3892/ol.2019.10518
  • Pages: 2102-2108
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Abstract

Tyrosine kinase inhibitors (TKIs), such as imatinib (IMA) and nilotinib (NIL), are the cornerstone of chronic myeloid leukemia (CML) treatment via the blockade of the oncogenic BCR‑ABL1 fusion protein. However, skeletal side effects are commonly observed in pediatric patients receiving long‑term treatment with IMA. Additionally, in vitro studies have shown that IMA and NIL alter vitamin D metabolism, which may further impair bone metabolism. To determine whether TKIs directly affect bone cell function, the present study treated the human osteoblastic cell line SaOS‑2 with IMA or NIL and assessed effects on their mineralization capacity as well as mRNA expression of receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG), two cytokines that regulate osteoclastogenesis. Both TKIs significantly inhibited mineralization and downregulated osteoblast marker genes, including alkaline phosphatase, osteocalcin, osterix, as well as genes associated with the pro‑osteogenic Wnt signaling pathway; NIL was more potent than IMA. In addition, both TKIs increased the RANKL/OPG ratio, which is known to stimulate osteoclastogenesis. The present results suggested that the TKIs IMA and NIL directly inhibited osteoblast differentiation and directly promoted a pro‑osteoclastogenic environment through the RANKL‑OPG signaling axis. Thus, we propose that future work is required to determine whether the bone health of CML patients undergoing TKI‑treatment should be routinely monitored.
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August-2019
Volume 18 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Kroschwald LM, Tauer JT, Kroschwald SI, Suttorp M, Wiedenfeld A, Beissert S, Bauer A and Rauner M: Imatinib mesylate and nilotinib decrease synthesis of bone matrix in vitro . Oncol Lett 18: 2102-2108, 2019.
APA
Kroschwald, L.M., Tauer, J.T., Kroschwald, S.I., Suttorp, M., Wiedenfeld, A., Beissert, S. ... Rauner, M. (2019). Imatinib mesylate and nilotinib decrease synthesis of bone matrix in vitro . Oncology Letters, 18, 2102-2108. https://doi.org/10.3892/ol.2019.10518
MLA
Kroschwald, L. M., Tauer, J. T., Kroschwald, S. I., Suttorp, M., Wiedenfeld, A., Beissert, S., Bauer, A., Rauner, M."Imatinib mesylate and nilotinib decrease synthesis of bone matrix in vitro ". Oncology Letters 18.2 (2019): 2102-2108.
Chicago
Kroschwald, L. M., Tauer, J. T., Kroschwald, S. I., Suttorp, M., Wiedenfeld, A., Beissert, S., Bauer, A., Rauner, M."Imatinib mesylate and nilotinib decrease synthesis of bone matrix in vitro ". Oncology Letters 18, no. 2 (2019): 2102-2108. https://doi.org/10.3892/ol.2019.10518