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Bone Destruction in Multiple Myeloma
Author(s) -
MATSUMOTO TOSHIO,
ABE MASAHIRO
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1346.035
Subject(s) - bone resorption , chemistry , bone marrow , osteoprotegerin , bone cell , microbiology and biotechnology , stromal cell , bone healing , osteoclast , osteopontin , cancer research , bone remodeling , osteoblast , endocrinology , medicine , receptor , biology , anatomy , biochemistry , in vitro , activator (genetics)
Multiple myeloma (MM) is characterized by accumulation of monoclonal plasma cells in the bone marrow and progression of lytic bone lesions. MM cells enhance bone resorption by triggering a coordinated increase in RANK ligand and decrease in osteoprotegerin in the bone marrow. Macrophage inflammatory protein (MIP)‐1α and (MIP)‐1β are secreted by MM cells, and play a major role in the enhancement of bone resorption by MM cells. Furthermore, the growth and survival of MM cells are enhanced by contact with osteoclasts (OCs) suggesting the presence of a vicious cycle between OCs and MM cells. OCs also enhance angiogenesis in concert with MM cells largely through the cooperative actions of osteopontin from OCs and VEGF from MM cells. The angiogenic effect may further facilitate the vicious cycle between bone destruction and MM cell expansion. In addition, MM cells secrete soluble factor(s) to suppress bone formation. Secreted Frizzled‐related protein (sFRP)‐2, an inhibitor of Wingless type (Wnt) binding to Frizzled, is produced by most MM cells, and immunodepletion of sFRP‐2 abrogates the inhibition of bone formation. Thus, MM cells enhance bone resorption and suppress bone formation to cause destructive bone lesions. Further elucidation of the mechanism of bone destruction by MM may lead to a novel therapeutic approach to prevent bone destruction and tumor growth.