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Stimulation of new bone formation by the proteasome inhibitor, bortezomib: implications for myeloma bone disease
Author(s) -
Oyajobi Babatunde O.,
Garrett I. Ross,
Gupta Anjana,
Flores Alda,
Esparza Javier,
Muñoz Steve,
Zhao Ming,
Mundy Gregory R.
Publication year - 2007
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2007.06829.x
Subject(s) - dkk1 , bortezomib , multiple myeloma , proteasome inhibitor , medicine , bone disease , bone marrow , cancer research , sclerostin , wnt signaling pathway , osteoporosis , oncology , chemistry , signal transduction , biochemistry
Summary 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.