Identification of new targets for therapy of osteolytic bone disease in multiple myeloma.
One of the most characteristic features of multiple myeloma is the development of osteolytic bone lesions. Myeloma-associated bone disease is caused by an increase in osteoclastic bone resorption and a decrease in osteoblastic new bone formation. Insight into the molecular mechanisms of osteoclastogenesis has been provided by the detection of receptor activator of NF-kappaB ligand (RANKL), its specific receptor (RANK) and its decoy receptor antagonist osteoprotegerin (OPG). The RANK signaling system is abnormally regulated in multiple myeloma and targeting this system may ameliorate myeloma bone disease. Less is known about the development of osteoblastic dysfunction, and further knowledge about the interaction between myeloma cells and osteoblasts is required. The aim of this review is to focus on the principles of bone biology for a better understanding of the development of myeloma bone disease and to identify possible therapeutic targets.
Hjertner
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Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. oyvind.hjertner@medisin.ntnu.no
Standal
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Børset
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Sundan
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Waage
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D016723:Bone Remodeling; D001862:Bone Resorption / Q000517:prevention & control; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000097:blood; D002454:Cell Differentiation; D004164:Diphosphonates / Q000627:therapeutic use; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000097:blood; D009101:Multiple Myeloma / Q000150:complications*; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology; D010010:Osteoclasts / Q000502:physiology; D010014:Osteolysis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood
D002352:Carrier Proteins; D004164:Diphosphonates; D006023:Glycoproteins; 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