Osteoprotegerin Reverses Osteoporosis by Inhibiting Endosteal Osteoclasts and Prevents Vascular Calcification by Blocking a Process Resembling Osteoclastogenesis
By Hosung Min, S. Morony, I. Sarosi, C. Dunstan, C. Capparelli, S. Scully, G. Van, S. Kaufman, P. Kostenuik, D. Lacey and 2 more. Journal of Experimental Medicine, 2000
599 citations recorded by the source corpus.
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.
Subfields: Molecular Biology, Oncology, Rheumatology
View Paper: https://www.semanticscholar.org/paper/c51ba8041e421a0dda85812324d9bd29d6295df7
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Citations in the corpus
- Changes in proinflammatory cytokine activity after menopause. (2002, background): “Estrogen dose dependently increased levels of OPG mRNA and protein in human osteoblastic cells (231) and stromal cells (232).”
- Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease. (2008, unknown): “Although OPG therapy consistently suppresses vascular calcification in animal models (127, 144, 166), there are minimal data on the effects of OPG therapy on atherogenesis or other aspects of vascular disease.”
- The molecular triad OPG/RANK/RANKL: involvement in the orchestration of pathophysiological bone remodeling. (2004, background): “OPG inhibits and prevents vascular calcification [35,184] Elevated OPG is associated with cardiovascular mortality in post-menauposal women [185]”
- Role of receptor activator of nuclear factor-κB ligand and osteoprotegerin in bone cell biology (2001, background): “Moreover, RANKL and RANK transcripts are expressed exclusively in the calcified arteries of OPG-deficient mice, not in wild-type mice [136].”