Osteoprotegerin Reverses Osteoporosis by Inhibiting Endosteal Osteoclasts and Prevents Vascular Calcification by Blocking a Process Resembling Osteoclastogenesis
| Autor: | Ildiko Sarosi, Sheila Scully, Colin R. Dunstan, Paul J. Kostenuik, Casey Capparelli, Sean Morony, W. Scott Simonet, David L. Lacey, William J. Boyle, Hosung Min, Gwyneth Van, Steve Kaufman |
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| Rok vydání: | 2000 |
| Předmět: |
Cathepsin K
Osteoclasts Receptors Cytoplasmic and Nuclear Pathologic calcification Receptors Tumor Necrosis Factor Mice Bone Density Cricetinae Immunology and Allergy Femur Aorta In Situ Hybridization Tartrate-resistant acid phosphatase Mice Knockout NF-kappa B Calcinosis vascular disease Immunohistochemistry Isoenzymes Arterial calcification Osteopetrosis Original Article musculoskeletal diseases Genetically modified mouse medicine.medical_specialty Recombinant Fusion Proteins Acid Phosphatase Blotting Western Immunology Mice Transgenic CHO Cells Osteoprotegerin Internal medicine medicine Animals Humans pathologic calcification Glycoproteins Cathepsin Tartrate-Resistant Acid Phosphatase business.industry medicine.disease osteoporosis Cathepsins Radiography Endocrinology atherosclerosis business |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | High systemic levels of osteoprotegerin (OPG) in OPG transgenic mice cause osteopetrosis with normal tooth eruption and bone elongation and inhibit the development and activity of endosteal, but not periosteal, osteoclasts. We demonstrate that both intravenous injection of recombinant OPG protein and transgenic overexpression of OPG in OPG−/2 mice effectively rescue the osteoporotic bone phenotype observed in OPG-deficient mice. However, intravenous injection of recombinant OPG over a 4-wk period could not reverse the arterial calcification observed in OPG−/− mice. In contrast, transgenic OPG delivered from mid-gestation through adulthood does prevent the formation of arterial calcification in OPG−/− mice. Although OPG is normally expressed in arteries, OPG ligand (OPGL) and receptor activator of NF-κB (RANK) are not detected in the arterial walls of wild-type adult mice. Interestingly, OPGL and RANK transcripts are detected in the calcified arteries of OPG−/− mice. Furthermore, RANK transcript expression coincides with the presence of multinuclear osteoclast-like cells. These findings indicate that the OPG/OPGL/RANK signaling pathway may play an important role in both pathological and physiological calcification processes. Such findings may also explain the observed high clinical incidence of vascular calcification in the osteoporotic patient population. |
| Databáze: | OpenAIRE |
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