New insight in the mechanism of osteoclast activation and formation in multiple myeloma: focus on the receptor activator of NF-kappaB ligand (RANKL).
The increase of osteoclast activation and formation is mainly involved in the development of the osteolytic bone lesions that characterize multiple myeloma (MM) patients. The mechanisms by which myeloma cells induce bone resorption have not been clear for many years. Recently, new evidence has elucidated which factors are critically involved in the activation of osteoclastic cells in MM. The potential role of the critical osteoclastogenic factor, the receptor activator of NF-kappaB ligand (RANKL), and its soluble antagonist osteoprotegerin (OPG) in the activation of bone resorption in MM is summarized in this review. It has been demonstrated that human MM cells induce an imbalance in the bone marrow environment of the RANKL/OPG ratio in favor of RANKL that triggers the osteoclast formation and activation leading to bone destruction. The direct production of the chemokine macrophage inflammatory protein-1 alpha (MIP-1alpha) by myeloma cells, in combination with the RANKL induction in BM stromal cells in response to myeloma cells, are critical in osteoclast activation and osteoclastogenesis.
Giuliani
Nicola
N
Hematology and BMT Unit, University of Parma, Italy. nicola.giuliani@unipr.it
Colla
Simona
S
Rizzoli
Vittorio
V
D000818:Animals; D001862:Bone Resorption / Q000209:etiology*; D002352:Carrier Proteins / Q000502:physiology*; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D004195:Disease Models, Animal; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D015851:Interleukin-7 / Q000502:physiology; D019402:Macrophage Inflammatory Proteins / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology*; D009101:Multiple Myeloma / Q000150:complications*; D010010:Osteoclasts / Q000502:physiology*; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor; D017154:Stromal Cells / Q000502:physiology
D002352:Carrier Proteins; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D006023:Glycoproteins; D015851:Interleukin-7; D019402:Macrophage Inflammatory Proteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human