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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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Submitted November 22, 2006
Accepted March 14, 2007
The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients
Nicola Giuliani*, Francesca Morandi, Sara Tagliaferri, Mirca Lazzaretti, Sabrina Bonomini, Monica Crugnola, Cristina Mancini, Eugenia Martella, Luca Ferrari, Antonio Tabilio, and Vittorio Rizzoli
Hematology & Bone Marrow Transplantation Center, Dept of Internal Medicine & Biomedical Science, University of Parma, Parma, Italy
Pathology, University of Parma, Parma, Italy
Hematology, University of Chieti, Chieti, Italy
* Corresponding author; email: n_giuliani{at}yahoo.com.
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  -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 responder 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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