Stimulation of new bone formation by the proteasome inhibitor, bortezomib: implications for myeloma bone disease.
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.
Oyajobi
Babatunde O
BO
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. oyajobi@uthscsa.edu
Garrett
I Ross
IR
Gupta
Anjana
A
Flores
Alda
A
Esparza
Javier
J
Muñoz
Steve
S
Zhao
Ming
M
Mundy
Gregory R
GR
D000818:Animals; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001897:Boronic Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000069286:Bortezomib; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D009924:Organ Culture Techniques; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D011480:Protease Inhibitors / Q000494:pharmacology*; D011719:Pyrazines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012886:Skull / Q000187:drug effects / Q000502:physiology
D000970:Antineoplastic Agents; D001897:Boronic Acids; C501127:Dkk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib