Abstract
Multiple myeloma (MM) is a plasma cell malignancy characterized by the high capacity to induce osteolytic bone lesions that mainly result from an increased bone resorption related to the stimulation of osteoclast recruitment and activity. Although it is known that myeloma cells induce osteoclastic bone resorption, the biological mechanisms involved in the pathophysiology of MM-induced bone resorption have been unclear for several years. Recently, new data seem to elucidate which mechanism is critically involved in the activation of osteoclastic cells in MM. The critical osteoclastogenetic factor RANKL and its soluble antagonist osteoprotegerin (OPG) are the major candidates in the pathophysiology of MM bone disease. Human MM cells induce an imbalance in the RANKL/OPG ratio in the bone marrow environment that triggers the osteoclast formation and activation leading to bone destruction. The role or RANKL/OPG system and other osteoclast stimulating factors in the pathophysiology of MM bone disease are summarized in this update.
MeSH terms
-
Animals
-
Bone Marrow / metabolism
-
Bone Resorption / etiology
-
Bone Resorption / physiopathology
-
Carrier Proteins / physiology
-
Cell Differentiation / drug effects
-
Cell Line, Tumor / metabolism
-
Chemokine CCL4
-
Culture Media, Conditioned / pharmacology
-
Cytokines / physiology
-
Glycoproteins / physiology
-
Humans
-
Interleukin-6 / physiology
-
Interleukin-7 / physiology
-
Macrophage Inflammatory Proteins / physiology
-
Membrane Glycoproteins / physiology
-
Mice
-
Multiple Myeloma / complications*
-
Multiple Myeloma / physiopathology
-
Neoplasm Proteins / physiology
-
Osteoblasts / physiology
-
Osteoclasts / metabolism
-
Osteoclasts / pathology
-
Osteolysis / etiology*
-
Osteoprotegerin
-
RANK Ligand
-
Receptor Activator of Nuclear Factor-kappa B
-
Receptors, Cytoplasmic and Nuclear / physiology
-
Receptors, Tumor Necrosis Factor
-
Stromal Cells / drug effects
-
Stromal Cells / metabolism
-
Stromal Cells / pathology
-
T-Lymphocyte Subsets / metabolism
Substances
-
Carrier Proteins
-
Chemokine CCL4
-
Culture Media, Conditioned
-
Cytokines
-
Glycoproteins
-
Interleukin-6
-
Interleukin-7
-
Macrophage Inflammatory Proteins
-
Membrane Glycoproteins
-
Neoplasm Proteins
-
Osteoprotegerin
-
RANK Ligand
-
Receptor Activator of Nuclear Factor-kappa B
-
Receptors, Cytoplasmic and Nuclear
-
Receptors, Tumor Necrosis Factor
-
TNFRSF11A protein, human
-
TNFRSF11B protein, human
-
TNFSF11 protein, human
-
Tnfrsf11a protein, mouse
-
Tnfrsf11b protein, mouse
-
Tnfsf11 protein, mouse