[Bone disease in multiple myeloma and its mechanism].
Multiple myeloma is characterized by accumulation of monoclonal plasma cells in the bone marrow and progression of lytic bone lesions. Myeloma cells enhance bone resorption by triggering a coordinated increase in RANK ligand and decrease in osteoprotegerin in the bone marrow. Macrophage inflammatory protein (MIP)-1alpha and MIP-1beta are secreted by myeloma cells, and play a major role in the enhancement of bone resorption by myeloma cells. Furthermore, the growth and survival of myeloma cells are enhanced by contact with osteoclasts, suggesting the presence of a vicious cycle between bone destruction and myeloma cell expansion. In addition, myeloma cells secrete soluble Wnt inhibitors, dickkopf (Dkk)-1 and secreted Frizzled-related protein (sFRP)-2, to suppress bone formation. Thus, myeloma cells closely interact with bone cells in the bone marrow microenvironment to enhance bone resorption and concomitantly suppress bone formation, which causes the formation of destructive bone lesions and a rapid loss of bone. Disruption of the pathognomonically skewed cellular interactions in myeloma bone marrow microenvironment may ameliorate bone destruction along with myeloma expansion.
University of Tokushima Graduate School of Medicine, Department of Medicine and Bioregulatory Sciences.
Masahiro
M
Abe
D001847:Bone Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D001862:Bone Resorption; D002352:Carrier Proteins / Q000502:physiology; D002454:Cell Differentiation; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000502:physiology; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology; D009101:Multiple Myeloma / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D010006:Osteoblasts / Q000166:cytology; D010010:Osteoclasts / Q000502:physiology; D010012:Osteogenesis; 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 / Q000502:physiology; D051153:Wnt Proteins / Q000502:physiology
C066507:CCL4 protein, human; D002352:Carrier Proteins; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019742:Chemokines, CC; D006023:Glycoproteins; 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; D051153:Wnt Proteins