[Osteoclast function is regulated by neighbouring osteoblasts. Osteoprotegerin, RAND and RANK ligand constitute a unique regulatory system for bone resorption with important pathophysiological and therapeutic aspects].
Maturation of macrophages to osteoclasts requires the presence of marrow stromal cells or osteoblasts. Most calcitropic hormones act indirectly on osteoclasts through receptors on neighbouring osteoblasts. The discovery of osteoprotegerin (OPG), the receptor activator of nuclear factor-kappa b ligand (RANKL), and its receptor (RANK) has elucidated these phenomena. It appears that osteoclast differentiation, activity, and survival are regulated by the proportion of inhibiting OPG to stimulating RANKL. OPG and RANKL are produced by osteoblasts, whereas RANK is located to the osteoclasts. Treatment with OPG inhibits bone resorption in postmenopausal women. Mutations in the system may be responsible for focal skeletal disorders. The discovery opens up for new treatment opportunities in postmenopausal and steroid-induced osteoporosis, Paget's disease, hypercalcaemia, and rheumatoid arthritis.
Rikshospitalet, Oslo.
Thor
T
Ueland
Jens
J
Bollerslev
Leif
L
Mosekilde
D016723:Bone Remodeling / Q000502:physiology*; D001862:Bone Resorption / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002470:Cell Survival; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D010006:Osteoblasts / Q000378:metabolism / Q000502:physiology*; D010010:Osteoclasts / Q000378:metabolism / Q000502:physiology*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D002352:Carrier Proteins; D006023:Glycoproteins; D018160:Receptors, Cytoplasmic and Nuclear