Osteoprogenitor differentiation is not affected by immunomodulatory thalidomide analogs but is promoted by low bortezomib concentration, while both agents suppress osteoclast differentiation

  • Authors:
    • Shoso Munemasa
    • Akira Sakai
    • Yoshiaki Kuroda
    • Yoshiko Okikawa
    • Yuta Katayama
    • Hideki Asaoku
    • Tadahiko Kubo
    • Shoji Shimose
    • Akiro Kimura
  • View Affiliations

  • Published online on: July 1, 2008     https://doi.org/10.3892/ijo.33.1.129
  • Pages: 129-136
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Abstract

We investigated the effects of bortezomib (PS-341) and immunomodulatory thalidomide analogs (immunomodulatory compounds; CC-4047, CC-6032, and CC-5013, or lenalidomide) on osteoblast and osteoclast differentiation in vitro using human mesenchymal stem cells (hMSC) to commit to osteoprogenitor cells and peripheral blood mononuclear cells (PBMCs) isolated from healthy donors, respectively. First, the concentration of bortezomib for an anti-myeloma effect was more than 1.0 nM in myeloma cells of multiple myeloma (MM) patients and more than 2.5 nM in myeloma cell lines. In contrast, anti-myeloma effects of immunomodulatory compounds on myeloma cells differed among myeloma cells and these compounds themselves. Subsequently, these agents (bortezomib; 0.5-5.0 nM, immunomodulatory compounds; 10 µM) were added to the osteoprogenitor cell culture media or the media for osteoclast differentiation. Low bortezomib concentrations (0.5 and 1.0 nM) increased ALP activity, and the delayed addition of bortezomib further increased ALP activity. Mineralized nodular formation with <2.5 nM bortezomib was not impaired. BMP2 expression on osteoprogenitor cells was found to increase in a time-dependent manner irrespective of treatment with bortezomib. On the other hand, the anti-osteoclast effect with low bortezomib concentration (≤2.5 nM) depended on MM patients. In contrast, immunomodulatory compounds at 10 µM showed an anti-osteoclast effect without cytotoxicity to osteoblast differentiation, at which dose myeloma cells underwent apoptosis. These findings might improve the treatment strategy for MM patients without damaging BM stromal cells by combining bortezomib with immunomodulatory compounds.

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July 2008
Volume 33 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Munemasa S, Sakai A, Kuroda Y, Okikawa Y, Katayama Y, Asaoku H, Kubo T, Shimose S and Kimura A: Osteoprogenitor differentiation is not affected by immunomodulatory thalidomide analogs but is promoted by low bortezomib concentration, while both agents suppress osteoclast differentiation. Int J Oncol 33: 129-136, 2008
APA
Munemasa, S., Sakai, A., Kuroda, Y., Okikawa, Y., Katayama, Y., Asaoku, H. ... Kimura, A. (2008). Osteoprogenitor differentiation is not affected by immunomodulatory thalidomide analogs but is promoted by low bortezomib concentration, while both agents suppress osteoclast differentiation. International Journal of Oncology, 33, 129-136. https://doi.org/10.3892/ijo.33.1.129
MLA
Munemasa, S., Sakai, A., Kuroda, Y., Okikawa, Y., Katayama, Y., Asaoku, H., Kubo, T., Shimose, S., Kimura, A."Osteoprogenitor differentiation is not affected by immunomodulatory thalidomide analogs but is promoted by low bortezomib concentration, while both agents suppress osteoclast differentiation". International Journal of Oncology 33.1 (2008): 129-136.
Chicago
Munemasa, S., Sakai, A., Kuroda, Y., Okikawa, Y., Katayama, Y., Asaoku, H., Kubo, T., Shimose, S., Kimura, A."Osteoprogenitor differentiation is not affected by immunomodulatory thalidomide analogs but is promoted by low bortezomib concentration, while both agents suppress osteoclast differentiation". International Journal of Oncology 33, no. 1 (2008): 129-136. https://doi.org/10.3892/ijo.33.1.129