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-κB ligand (RANKL) and decreasing osteoproteger...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical and biophysical research communications 2005-12, Vol.338 (2), p.687-693
Main Authors: Heider, Ulrike, Hofbauer, Lorenz C., Zavrski, Ivana, Kaiser, Martin, Jakob, Christian, Sezer, Orhan
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - administration & dosage
Bone Neoplasms - drug therapy
Bone Neoplasms - immunology
Bone Remodeling - drug effects
Bone Remodeling - immunology
Drug Delivery Systems - methods
Humans
Multiple Myeloma - drug therapy
Multiple Myeloma - immunology
Myeloma bone disease
Osteoblasts
Osteoblasts - drug effects
Osteoblasts - immunology
Osteoclast
RANKL
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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-κB 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-1α, MIP-1β, and SDF-1α, 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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2005.09.146