Evidence of a role for RANKL in the development of myeloma bone disease.
Multiple myeloma is associated with the development of a devastating bone disease mediated by increased osteoclastic activity. The ligand for receptor activator of nuclear factor-kappaB (RANKL) plays a critical role in normal osteoclast biology and is abnormally regulated in myeloma. Targeting this system with recombinant decoy receptor, osteoprotegerin, or soluble forms of the receptor activator of nuclear factor-kappaB is able to prevent myeloma bone disease in pre-clinical models. Intriguingly, inhibiting osteoclast formation and bone resorption, and altering the bone marrow microenvironment, results in an indirect anti-myeloma effect.
De Leenheer
Evy
E
Bone Biology Group, G Floor, Division of Clinical Sciences, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
Mueller
Gabrielle S
GS
Vanderkerken
Karin
K
Croucher
Peter I
PI
D000818:Animals; D001862:Bone Resorption / Q000209:etiology*; D002352:Carrier Proteins / Q000502:physiology*; D006023:Glycoproteins / Q000502:physiology / Q000627:therapeutic use; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D009101:Multiple Myeloma / Q000150:complications* / Q000188:drug therapy; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology / Q000627:therapeutic use; 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