Role of RANKL and RANK in bone loss and arthritis.
The tumour necrosis factor family molecule RANKL (RANKL, TRANCE, ODF) and its receptor RANK are key regulators of bone remodelling and regulate T cell/dendritic cell communications, and lymph node formation. Moreover, RANKL and RANK are expressed in mammary gland epithelial cells and control the development of a lactating mammary gland during pregnancy and the propagation of mammalian species. Importantly, RANKL and RANK are essential for the development and activation of osteoclasts and bone loss in response to virtually all triggers tested. Therapeutically, inhibition of RANKL function via the decoy receptor osteoprotegerin completely prevents bone loss at inflammed joints and has partially beneficial effects on cartilage destruction in all arthritis models studied. Modulation of these systems provides a unique opportunity to design novel treatments to inhibit bone loss and crippling in arthritis.
Jones
D Holstead
DH
Institute for Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.
Kong
Y-Y
YY
Penninger
J M
JM
D000818:Animals; D001168:Arthritis / Q000503:physiopathology*; D002352:Carrier Proteins / Q000502:physiology*; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D007107:Immune System / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology*; D010010:Osteoclasts / Q000502:physiology; D010024:Osteoporosis / Q000503:physiopathology*; 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; D013601:T-Lymphocytes / Q000276:immunology
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