[Bone remodeling and mineral homeostasis].
The discovery of receptor activator of nuclear factor-kappaB ligand (RANKL) elucidates the mechanism of osteoclast differentiation and function regulated by osteoblasts. Osteoprotegerin (OPG), a soluble decoy receptor of RANKL, inhibits both differentiation and function of osteoclasts. OPG-deficient (OPG-/-) mice exhibited severe osteoporosis caused by enhanced osteoclastic bone resorption. Deficiency of OPG in human has been shown to result in juvenile Paget's disease. Blood alkaline phosphatase activity of OPG-/- mice was about four times as high as that of wild-type mice. These results suggest that osteoclastic bone resorption coincidentally induces osteoblastic bone formation by an unknown factor (called coupling factor). Collagen sponge disks containing bone morphogenetic protein-2 (rhBMP-2) were implanted into the dorsal muscle pouches in OPG-/- mice and wild-type mice, and bone mineral density (BMD) of the collagen sponge disks was determined every week for 3 weeks. No significant difference in BMD of the disc was observed between OPG-/- mice and wild-type mice. These results suggest that bone formation is accurately coupled with bone resorption at local sites in OPG-/- mice.
Nakamura
Midori
M
Department of Biochemistry, Matsumoto Dental University.
Udagawa
Nobuyuki
N
Nakamura
Hiroshi
H
D000818:Animals; D015519:Bone Density; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D016723:Bone Remodeling / Q000502:physiology*; D002352:Carrier Proteins / Q000096:biosynthesis; D002454:Cell Differentiation; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics
D019485:Bone Morphogenetic Proteins; 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; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C505689:Tnfsf11 protein, mouse