[Stimulation of new bone formation by the proteasome inhibitor, bortezomib: implications for myeloma bone disease]
>>Br J Haematol. 2007 Nov;139(3):434-8.
Stimulation of new bone formation by the proteasome inhibitor, bortezomib: implications for myeloma bone disease.
Oyajobi BO, Garrett IR, Gupta A, Flores A, Esparza J, Muñoz S, Zhao M, Mundy GR.
Department of Cellular and Structural Biology University of Texas Health Science Center at San Antonio, San Antonio, TX, USA, and San Antonio Cancer Institute, San Antonio, TX, USA.
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.<<
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