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 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.

The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients / Giuliani, Nicola; Morandi, F; Tagliaferri, Sara; Lazzaretti, Mirca; Bonomini, S; Crugnola, M; Mancini, C; Martella, E; Ferrari, L; Tabilio, A; Rizzoli, Vittorio. - In: BLOOD. - ISSN 0006-4971. - 110:(2007), pp. 334-338. [10.1182/blood-2006-11-059188]

The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients

GIULIANI, Nicola;TAGLIAFERRI, Sara;LAZZARETTI, Mirca;RIZZOLI, Vittorio
2007-01-01

Abstract

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 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.
2007
The proteasome inhibitor bortezomib affects osteoblast differentiation in vitro and in vivo in multiple myeloma patients / Giuliani, Nicola; Morandi, F; Tagliaferri, Sara; Lazzaretti, Mirca; Bonomini, S; Crugnola, M; Mancini, C; Martella, E; Ferrari, L; Tabilio, A; Rizzoli, Vittorio. - In: BLOOD. - ISSN 0006-4971. - 110:(2007), pp. 334-338. [10.1182/blood-2006-11-059188]
File in questo prodotto:
File Dimensione Formato  
PAPER 2 ANVUR.pdf

non disponibili

Tipologia: Documento in Post-print
Licenza: Creative commons
Dimensione 229.04 kB
Formato Adobe PDF
229.04 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2295213
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 230
  • ???jsp.display-item.citation.isi??? 204
social impact