Abstract
Impaired bone formation contributes to the lack of bone healing in multiple myeloma and there is a need for agents with bone anabolic properties to reverse the bone deficit in patients. Bortezomib, a proteasome inhibitor with antitumour efficacy in myeloma patients, enhanced new bone formation in mouse calvarial cultures; this effect was blocked by dickkopf 1(Dkk1), an antagonist of Wnt signalling implicated in myeloma bone disease. Bortezomib inhibited Dkk1 expression in calvariae and bone marrow-derived stromal cells, suggesting a novel mechanism by which bortezomib exerts its effects in bone. Clinical trials in patients with myeloma bone disease are needed to validate these results.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antineoplastic Agents / antagonists & inhibitors
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Antineoplastic Agents / pharmacology*
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Boronic Acids / antagonists & inhibitors
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Boronic Acids / pharmacology*
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Bortezomib
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Cell Differentiation / drug effects
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Dose-Response Relationship, Drug
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Intercellular Signaling Peptides and Proteins / pharmacology
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Mice
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Mice, Inbred ICR
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Organ Culture Techniques
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Osteoblasts / cytology
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Osteoblasts / drug effects
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Osteogenesis / drug effects*
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Protease Inhibitors / pharmacology*
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Pyrazines / antagonists & inhibitors
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Pyrazines / pharmacology*
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Reverse Transcriptase Polymerase Chain Reaction / methods
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Skull / drug effects
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Skull / physiology
Substances
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Antineoplastic Agents
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Boronic Acids
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Dkk1 protein, mouse
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Intercellular Signaling Peptides and Proteins
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Protease Inhibitors
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Pyrazines
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Bortezomib