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Blood, 1 July 2007, Vol. 110, No. 1, pp. 334-338.
Prepublished online as a Blood First Edition Paper on March 19, 2007; DOI 10.1182/blood-2006-11-059188.
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NEOPLASIA
The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients
Nicola Giuliani1,
Francesca Morandi1,
Sara Tagliaferri1,
Mirca Lazzaretti2,
Sabrina Bonomini1,
Monica Crugnola1,
Cristina Mancini2,
Eugenia Martella2,
Luca Ferrari1,
Antonio Tabilio3, and
Vittorio Rizzoli1
1 Hematology and Bone Marrow Transplantation Center, Department of Internal Medicine and Biomedical Science, University of Parma, Italy;
2 Pathology, University of Parma, Italy;
3 Department of Internal Medicine and Public Health, University of Chieti, Italy
The proteasome inhibitor bortezomib may increase osteoblast-related markers in multiple myeloma (MM) patients; however, its potential osteoblastic stimulatory effect is not known. In this study, we show that bortezomib significantly induced a stimulatory effect on osteoblast markers in human mesenchymal cells without affecting the number of osteoblast progenitors in bone marrow cultures or the viability of mature osteoblasts. Consistently we found that bortezomib significantly increased the transcription factor Runx2/Cbfa1 activity in human osteoblast progenitors and osteoblasts without affecting nuclear and cytoplasmatic active ß-catenin levels. Consequently a stimulatory effect of bortezomib on bone nodule formation was also demonstrated in osteoblast progenitors. These in vitro observations were confirmed in vivo by the finding of a significant increase in the number of osteoblastic cells x mm2 of bone tissue and in the number of Runx2/Cbfa1-positive osteoblastic cells that was observed in MM patients who responded to bortezomib. Our in vitro and in vivo observations support the hypothesis that a direct stimulatory effect on bone formation process could occur during bortezomib treatment.
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