Novel aspects of osteoclast activation and osteoblast inhibition in myeloma bone disease.
Increased bone resorption is a major characteristic of multiple myeloma and is caused by osteoclast activation and osteoblast inhibition (uncoupling). Myeloma cells alter the local regulation of bone metabolism by increasing the receptor activator of NF-kappaB ligand (RANKL) and decreasing osteoprotegerin expression within the bone marrow microenvironment, thereby stimulating the central pathway for osteoclast formation and activation. In addition, they produce the chemokines MIP-1alpha, MIP-1beta, and SDF-1alpha, which also increase osteoclast activity. On the other hand, myeloma cells suppress osteoblast function by the secretion of osteoblast inhibiting factors, e.g., the Wnt inhibitors DKK-1 and sFRP-2. Moreover, they inhibit differentiation of osteoblast precursors and induce apoptosis in osteoblasts. The resulting bone destruction releases several cytokines, which in turn promote myeloma cell growth. Therefore, the inhibition of bone resorption could stop this vicious circle and not only decrease myeloma bone disease, but also the tumor progression.
Heider
Ulrike
U
Department of Oncology and Hematology, University Hospital Charité, D-10117 Berlin, Germany.
Hofbauer
Lorenz C
LC
Zavrski
Ivana
I
Kaiser
Martin
M
Jakob
Christian
C
Sezer
Orhan
O
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D016723:Bone Remodeling / Q000187:drug effects / Q000276:immunology; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology*; D010006:Osteoblasts / Q000187:drug effects* / Q000276:immunology*
D000970:Antineoplastic Agents