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KMID : 0438420070140020109
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Korean Journal of Bone Metabolism
2007 Volume.14 No. 2 p.109 ~ p.115
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Clinical Implications of the Osteoprotegerin and Receptor Activator of NF-κB Ligand System for Bone Metabolism and Vascular Diseases
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Oh Ki-Won
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Abstract
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Osteoprotegerin (OPG) is a glycoprotein that is a member of the tumor necrosis factor receptor (TNFR) superfamily, and is known to inhibit osteoclastogenesis by acting as a decoy receptor for the receptor activator of NF-κB ligand (RANKL), thus blocking the differentiation of osteoclasts. Mice with overexpression of the OPG gene show typical osteopetrosis and severe atrophy of marrow tissues. OPG is strongly expressed not only in skeletal tissues but also in the heart and in the walls of large vessels. OPG knockout mice show severe osteoporosis with calcification in the aorta and renal arteries, and these abnormalities can be prevented by concurrent transgenic overexpression of OPG, suggesting the possibility that OPG has a role in the cross-talk between vessel and bone relative to calcium metabolism. Interestingly, recombinant OPG treatment in animals prevented arterial calcifications provoked by warfarin or high doses of vitamin D. OPG and RANKL are expressed in the arterial wall by smooth muscle and endothelial cells. Some studies suggest that RANKL and OPG modulate apoptosis of endothelial cells, which may affect the integrity of the vessel lumen. In human studies, serum levels of OPG concentration has been reported to be significantly related to the severity of coronary artery disease, the risk for diabetes mellitus and its complication, and osteoporosis, suggesting that its role in relation to bone metabolism and vascular biology in humans may be similar to that observed in animal models. OPG polymorphisms have been studied relative to bone mineral density, osteoporotic fracture and intima-media thickness (IMT), which is a risk factor for cardiovascular diseases, and linkage of genetic variations in the OPG gene with increased risk for coronary artery disease has been reported. Also, RANKL blockade has prevented bone loss caused by osteoporosis in animal models and may emerge as a therapy in humans based on studies in postmenopausal osteoporosis. [Korean Journal of Bone Metabolism, 14(2): 109-115, 2007]
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KEYWORD
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Osteoprotegerin, Receptor activator of NF-κB ligand, Bone metabolism, Vascular diseases
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