Receptor activator for nuclear factor kappaB ligand and osteoprotegerin: regulators of bone physiology and immune responses/potential therapeutic agents and biochemical markers.
The discovery of receptor activator for nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) as the fundamental factors in controlling osteoclast formation and activation has led to a greater understanding of bone biology over the past few years. Here we discuss the role of these molecules in immunology and skeletal remodelling and assess their involvement in diseases of bones and joints, including rheumatoid arthritis, Paget's disease, post-menopausal osteoporosis and malignant bone diseases. OPG has been identified as a potential anabolic agent for treating conditions in which there is net bone loss and is currently in Phase I clinical trials. This review examines the current evidence indicating that OPG increases bone mass, and discusses other possible beneficial effects of OPG, such as inhibition of tumour growth and relief from bone cancer pain. OPG can be measured in human serum, and numerous studies have suggested that increased or decreased serum concentrations of this molecule can indicate the existence of remodelling disorders. Here we discuss how abnormal serum OPG concentrations could potentially be used to indicate imbalances of bone resorption and formation. The possible applications of serum OPG concentration as a marker for non-skeletal disease conditions are also considered.
Buckley
Katherine A
KA
Human Bone Cell Research Group, Department of Human Anatomy and Cell Biology, The Sherrington Buildings University of Liverpool Liverpool L69 3GE, UK.
Fraser
William D
WD
D015415:Biomarkers / Q000097:blood; D001847:Bone Diseases / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D006023:Glycoproteins / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D007592:Joint Diseases / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D018124:Receptors, Tumor Necrosis Factor
D015415:Biomarkers; 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