Abstract
Deficiency of osteoprotegerin (OPG), a soluble decoy receptor for receptor activator of nuclear factor-kappaB ligand (RANKL), in mice induces osteoporosis caused by enhanced bone resorption, but also accelerates bone formation. We examined whether bone formation is coupled with bone resorption in OPG-deficient (OPG-/-) mice using risedronate, an inhibitor of bone resorption. Histomorphometric analysis showed that bone formation-related parameters (e.g. mineral apposition rate and osteoblast surface/bone surface) in OPG-/- mice sharply decreased with suppression of bone resorption by daily injection of risedronate for 30 d. OPG-/- mice exhibited high serum alkaline phosphatase activity and osteocalcin concentration, both of which were decreased to the levels in wild-type mice by the risedronate injection. Serum levels of RANKL were markedly elevated in OPG-/- mice, but were unaffected by risedronate. The ectopic bone formation induced by bone morphogenetic protein-2 implantation into OPG-/- mice was not accelerated even with a high turnover rate of bone, but attenuation of mineral density from the ectopic bone was more pronounced than that in wild-type mice. These results suggest that bone formation is coupled with bone resorption at local sites in OPG-/- mice, and that serum RANKL levels do not reflect this coupling.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins / pharmacology
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Bone Resorption / drug therapy
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Bone Resorption / pathology
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Bone Resorption / physiopathology*
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Bone and Bones / cytology
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Bone and Bones / drug effects
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Bone and Bones / metabolism
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Calcium / blood
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Calcium Channel Blockers / pharmacology
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Carrier Proteins / blood
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Etidronic Acid / analogs & derivatives*
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Etidronic Acid / pharmacology
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Glycoproteins / genetics*
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Glycoproteins / metabolism*
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Male
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Membrane Glycoproteins / blood
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Mice
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Mice, Inbred C57BL
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Mice, Mutant Strains
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Osteocalcin / blood
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Osteogenesis / physiology*
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Osteoprotegerin
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Phosphorus / blood
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RANK Ligand
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Receptor Activator of Nuclear Factor-kappa B
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Receptors, Cytoplasmic and Nuclear / genetics*
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Receptors, Cytoplasmic and Nuclear / metabolism*
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Receptors, Tumor Necrosis Factor
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Risedronic Acid
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Transforming Growth Factor beta*
Substances
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Bmp2 protein, mouse
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Bone Morphogenetic Protein 2
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Bone Morphogenetic Proteins
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Calcium Channel Blockers
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Carrier Proteins
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Glycoproteins
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Membrane Glycoproteins
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Osteoprotegerin
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RANK Ligand
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Receptor Activator of Nuclear Factor-kappa B
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Receptors, Cytoplasmic and Nuclear
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Receptors, Tumor Necrosis Factor
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Tnfrsf11a protein, mouse
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Tnfrsf11b protein, mouse
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Tnfsf11 protein, mouse
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Transforming Growth Factor beta
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Osteocalcin
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Phosphorus
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Risedronic Acid
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Etidronic Acid
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Calcium