Bone cancer pain and the role of RANKL/OPG.
Cancer-induced bone diseases are common and can have a devastating impact at the end of life. One of the most difficult sequelae of cancer is metastases to the skeleton, an event that results in bone destruction and bone cancer pain. Bone cancer pain is usually progressive as the disease advances, and is particularly difficult to treat. Recently, experimental models of bone cancer pain have been developed and have provided seminal insight in understanding the pathophysiology of bone cancer pain. Animal models of bone cancer provided the finding that bone destruction (osteolysis) is associated with pain, and it has been determined that cancer-induced osteolysis is mediated by osteoclasts. Having established that RANK ligand contributed to cancer-induced osteoclastogenesis, it was determined that disruption of the RANKL-RANK axis with OPG inhibited tumor-induced osteoclastogenesis and decreased bone cancer pain.
Clohisy
D R
DR
Dept of Orthopaedic Surgery, University of Minnesota, Minneapolis, MN 55455, USA. clohi001@umn.edu
Mantyh
P W
PW
D001859:Bone Neoplasms / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D002352:Carrier Proteins / Q000502:physiology*; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D053244:Osteoprotegerin; D010146:Pain / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor
D002352:Carrier Proteins; 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