The osteoprotegerin/RANK/RANKL system: a bone key to vascular disease

References

• Aukrust P, Yndestad A, Waehre T, Gullestad L, Halvorsen B, Damas JK. Inflammation in coronary artery disease. Potential role for immunomodulatory therapy. Expert Rev. Cardiovasc. Ther.3, 1111–1124 (2005).
   PubMedGoogle Scholar
• Wick G, Knoflach M, Xu Q. Autoimmune and inflammatory mechanisms in atherosclerosis. Annu. Rev. Immunol.22, 361–403 (2004).
   PubMed Web of Science ®Google Scholar
• Kiechl S, Lorenz E, Reindl M et al. Toll-like receptor 4 polymorphisms and atherogenesis. N. Engl. J. Med.347, 185–192 (2002).
   PubMed Web of Science ®Google Scholar
• Karsenty G. The complexities of skeletal biology. Nature423, 316–318 (2003).
   PubMed Web of Science ®Google Scholar
• Schett G, Kiechl S, Redlich K et al. Soluble RANKL and risk of nontraumatic fracture. JAMA291, 1108–1113 (2004).
   PubMed Web of Science ®Google Scholar
• Teitelbaum SL. Bone resorption by osteoclasts. Science289, 1504–1508 (2000).
   PubMed Web of Science ®Google Scholar
• Anderson DM, Maraskovsky E, Billingsley WL et al. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature390, 175–179 (1997).
   PubMed Web of Science ®Google Scholar
• Lacey DL, Timms E, Tan HL et al. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell93, 165–176 (1998).
   PubMed Web of Science ®Google Scholar
• Yasuda H, Shima N, Nakagawa N et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc. Natl Acad. Sci. USA95, 3597–3602 (1998).
   PubMed Web of Science ®Google Scholar
• Kong YY, Yoshida H, Sarosi I et al. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature397, 315–323 (1999).
   PubMed Web of Science ®Google Scholar
• Goldring SR. Inflammatory mediators as essential elements in bone remodeling. Calcif. Tissue Int.73, 97–100 (2003).
   PubMed Web of Science ®Google Scholar
• Sezer O. Myeloma bone disease. Hematology10(Suppl. 1), 19–24 (2005).
   PubMed Web of Science ®Google Scholar
• Blair JM, Zhou H, Seibel MJ, Dunstan CR. Mechanisms of disease. Roles of OPG, RANKL and RANK in the pathophysiology of skeletal metastasis. Nat. Clin. Pract. Oncol.3, 41–49 (2006).
   PubMedGoogle Scholar
• Canalis E. Mechanisms of glucocorticoid action in bone. Curr. Osteoporos. Rep.3, 98–102 (2005).
   PubMedGoogle Scholar
• Grigoriadis AE, Wang ZQ, Cecchini MG et al. c-Fos: a key regulator of osteoclast–macrophage lineage determination and bone remodeling. Science266, 443–448 (1994).
   PubMed Web of Science ®Google Scholar
• Wada T, Nakashima T, Oliveira-dos-Santos AJ et al. The molecular scaffold Gab2 is a crucial component of RANK signaling and osteoclastogenesis. Nat. Med.11, 394–399 (2005).
   PubMed Web of Science ®Google Scholar
• Ruocco MG, Maeda S, Park JM et al. IκB kinase (IKK)β, but not IKKα, is a critical mediator of osteoclast survival and is required for inflammation-induced bone loss. J. Exp. Med.201, 1677–1687 (2005).
   PubMed Web of Science ®Google Scholar
• Hsu H, Lacey DL, Dunstan CR et al. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc. Natl Acad. Sci. USA96, 3540–3545 (1999).
   PubMed Web of Science ®Google Scholar
• Jones DH, Nakashima T, Sanchez OH. Regulation of cancer cell migration and bone metastasis by RANKL. Nature440, 692–696 (2006).
   PubMed Web of Science ®Google Scholar
• Truneh A, Sharma S, Silverman C et al. Temperature-sensitive differential affinity of TRAIL for its receptors. DR5 is the highest affinity receptor. J. Biol. Chem.275, 23319–23325 (2000).
   PubMed Web of Science ®Google Scholar
• Simonet WS, Lacey DL, Dunstan CR et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell89, 309–319 (1997).
   PubMed Web of Science ®Google Scholar
• Rasmussen LM, Ledet T. Osteoprotegerin and diabetic macroangiopathy. Horm. Metab. Res.37(Suppl. 1), 90–94 (2005).
   PubMedGoogle Scholar
• Olesen P, Ledet T, Rasmussen LM. Arterial osteoprotegerin: increased amounts in diabetes and modifiable synthesis from vascular smooth muscle cells by insulin and TNF-α. Diabetologia48, 561–568 (2005).
   PubMed Web of Science ®Google Scholar
• Kiechl S, Schett G, Wenning G et al. Osteoprotegerin is a risk factor for progressive atherosclerosis and cardiovascular disease. Circulation109, 2175–2180 (2004).
   PubMed Web of Science ®Google Scholar
• Crisafulli A, Micari A, Altavilla D et al. Serum levels of osteoprotegerin and RANKL in patients with ST elevation acute myocardial infarction. Clin. Sci.109, 389–395 (2005).
   PubMed Web of Science ®Google Scholar
• Sandberg WJ, Yndestad A, Oie E et al. Enhanced T-cell expression of RANK ligand in acute coronary syndrome: possible role in plaque destabilization. Arterioscler. Thromb. Vasc. Biol.26, 857–863 (2006).
   PubMed Web of Science ®Google Scholar
• Schoppet M, Sattler AM, Schaefer JR, Herzum M, Maisch B, Hofbauer LC. Increased osteoprotegerin serum levels in men with coronary artery disease. J. Clin. Endocrinol. Metab.88, 1024–1028 (2003).
   PubMed Web of Science ®Google Scholar
• Kazama J, Shigematsu T, Yano K et al. Increased circulating levels of osteoclastogenesis inhibitory factor (osteoprotegerin) in patients with chronic renal failure. Am. J. Kidney Dis.39, 525–232 (2002).
   PubMed Web of Science ®Google Scholar
• Hermann-Arnhof KM, Kastenbauer T, Publig T et al. Initially elevated osteoprotegerin serum levels may predict a perioperative myocardial lesion in patients undergoing coronary artery bypass grafting. Crit. Care Med.34, 76–80 (2006).
   PubMedGoogle Scholar
• Rasmussen LM, Tarnow L, Hansen TK, Parving H-H, Flyvbjerg A. Plasma osteoprotegerin levels are associated with glycaemic status, systolic blood pressure, kidney function and cardiovascular morbidity in type 1 diabetic patients. Eur. J. Endocrinol.154, 75–81 (2006).
   PubMed Web of Science ®Google Scholar
• Oh ES, Rhee EJ, Oh KW et al. Circulating osteoprotegerin levels are associated with age, waist-to-hip ratio, serum total cholesterol, and low-density lipoprotein cholesterol levels in healthy Korean women. Metabolism54, 49–54 (2005).
   PubMed Web of Science ®Google Scholar
• Nagasaki T, Inaba M, Jono S et al. Increased levels of serum osteoprotegerin in hypothyroid patients and its normalization with restoration of normal thyroid function. Eur. J. Endocrinol.152, 347–353 (2005).
   PubMedGoogle Scholar
• Avbersek-Luznik I, Malesic I, Rus I, Marc J. Increased levels of osteoprotegerin in hemodialysis patients. Clin. Chem. Lab. Med.40, 1019–1023 (2002).
   PubMedGoogle Scholar
• Collin-Osdoby P. Regulation of vascular calcification by osteoclast regulatory factors RANKL and osteoprotegerin. Circ. Res.95, 1046–1057 (2004).
   PubMed Web of Science ®Google Scholar
• Hofbauer LC, Schoppet M. Serum measurement of osteoprotegerin: clinical relevance of potential applications. Eur. J. Endocrinol.145, 681–683 (2001).
   PubMedGoogle Scholar
• Ueland T, Jemtland R, Godang K et al. Prognostic value of osteoprotegerin in heart failure after acute myocardial infarction. J. Am. Coll. Cardiol.16, 1970–1976 (2004).
   Google Scholar
• Rhee EJ, Lee WY, Kim SY et al. Relationship of serum osteoprotegerin levels with coronary artery disease severity, left ventricular hypertrophy and C-reactive protein. Clin. Sci.108, 237–243 (2005).
   PubMed Web of Science ®Google Scholar
• Kim SM, Lee J, Ryu OH et al. Serum osteoprotegerin levels are associated with inflammation and pulse wave velocity. Clin. Endocrinol.63, 594–598 (2005).
   PubMed Web of Science ®Google Scholar
• Vik A, Mathiesen EB, Noto AT, Sveinbjornsson B, Brox J, Hansen JB. Serum osteoprotegerin is inversely associated with carotid plaque echogenicity in humans. Atherosclerosis DOI: 10.1016/j.atherosclerosis.2006.03.002 (2006) (Epub ahead of print).
   PubMedGoogle Scholar
• Browner WS, Lui L, Cummings SR. Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women. J. Clin. Endocrinol. Metab.86, 631–637 (2001).
   PubMed Web of Science ®Google Scholar
• Knudsen S, Foss C, Poulsen P, Anderson N, Mogensen C, Rasmussen L. Increased plasma concentrations of osteoprotegerin in type 2 diabetic patients with microvascular complications. Eur. J. Endocrinol.149, 39–42 (2003).
   PubMed Web of Science ®Google Scholar
• Dhore CR, Cleutjens JPM, Lutgens E et al. Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques. Arterioscler. Thromb. Vasc. Biol.21, 1998–2003 (2001).
   PubMed Web of Science ®Google Scholar
• Shanahan CM, Cary NR, Salisbury JR, Proudfoot D, Weissberg PL, Edmonds ME. Medial localization of mineralization-regulating proteins in association with Monckeberg’s sclerosis: evidence for smooth muscle cell-mediated vascular calcification. Circulation100, 2168–2176 (1999).
   PubMed Web of Science ®Google Scholar
• Tyson KL, Reynolds JL, McNair R, Zhang Q, Weissberg PL, Shanahan R. Osteo/chondrocytic transcription factors and their target genes exhibit distinct patterns of expression in human arterial calcification. Arterioscler. Thromb. Vasc. Biol.23, 489–494 (2003).
   PubMed Web of Science ®Google Scholar
• Tintut Y, Demer LL. Recent advances in multifactorial regulation of vascular calcification. Curr. Opin. Lipidol.12, 555–560 (2001).
   PubMed Web of Science ®Google Scholar
• Vattikuti R, Towler DA. Osteogenic regulation of vascular calcification: an early perspective. Am. J. Physiol. Endocrinol. Metab.286, E686–E696 (2004).
   PubMed Web of Science ®Google Scholar
• Bucay N, Sarosi I, Dunstan CR et al. Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev.12, 1260–1268 (1998).
   PubMed Web of Science ®Google Scholar
• Min H, Morony S, Sarosi I et al. Osteoprotegerin reverses osteoporosis by inhibiting endosteal osteoclasts and prevents vascular calcification by blocking a process resembling osteoclastogenesis. J. Exp. Med.192, 463–474 (2000).
   PubMed Web of Science ®Google Scholar
• Price PA, June HH, Buckley JR, Williamson MK. Osteoprotegerin inhibits artery calcification induced by warfarin and by vitamin D. Arterioscler. Thromb. Vasc. Biol.21, 1610–1616 (2001).
   PubMed Web of Science ®Google Scholar
• Brändström H, Stiger F, Lind L, Kahan T, Melhus H, Kindmark A. A single nucleotide polymorphism in the promoter region of the human gene for osteoprotegerin is related to vascular morphology and function. Biochem. Biophys. Res. Commun.234, 137–142 (1997).
   PubMedGoogle Scholar
• Jono S, Shioi A, Ikari Y, Nishizawa Y. Vascular calcification in chronic kidney disease. J. Bone Miner. Metab.24, 176–181 (2006).
   PubMed Web of Science ®Google Scholar
• Nitta K, Akiba T, Uchida K et al. Serum osteoprotegerin levels and the extent of vascular calcification in haemodialysis patients. Nephrol. Dial. Transplant.19, 1886–1889 (2004).
   PubMed Web of Science ®Google Scholar
• Schoppet M, Al Fakhri N, Franke FE et al. Localization of osteoprotegerin, tumor necrosis factor-related apoptosis-including ligand, and receptor activator of nuclear factor-κB ligand in Monckeberg’s sclerosis and atherosclerosis. J. Clin. Endocrinol. Metabol.89, 4104–4112 (2004).
   PubMed Web of Science ®Google Scholar
• Hunt JL, Fairman R, Mitchell ME et al. Bone formation in carotid plaques: a clinicopathological study. Stroke33, 1214–1219 (2002).
   PubMed Web of Science ®Google Scholar
• Beckman JA, Ganz J, Creager MA, Ganz P, Kinlay S. Relationship of clinical presentation and calcification of culprit coronary artery stenoses. Arterioscler. Thromb. Vasc. Biol.21, 1618–1622 (2001).
   PubMedGoogle Scholar
• Huang H, Virmani R, Younis H, Burke AP, Kamm RD, Lee RT. The impact of calcification on the biomechanical stability of atherosclerotic plaques. Circulation103, 1051–1056 (2001).
   PubMed Web of Science ®Google Scholar
• Moran CS, McCann M, Karan M, Norman P, Ketheesan N, Golledge J. Association of osteoprotegerin with human abdominal aortic aneurysm progression. Circulation111, 3119–3125 (2005).
   PubMedGoogle Scholar
• Ueland T, Yndestad A, Øie E et al. Dysregulated osteoprotegerin/RANK ligand/RANK axis in clinical and experimental heart failure. Circulation111, 2461–2468 (2005).
   PubMed Web of Science ®Google Scholar
• Hofbauer L, Schoppet M. Clinical implications of the osteoprotegerin/RANKL/RANK system for bone and vascular disease. JAMA292, 490–495 (2004).
   PubMed Web of Science ®Google Scholar
• Golledge J, McCann M, Mangan S, Lam A, Karan M. Osteoprotegerin and osteopontin are expressed at high concentrations within symptomatic carotid atherosclerosis. Stroke35, 1636–1641 (2004).
   PubMed Web of Science ®Google Scholar
• Mahamed DA, Marleau A, Alnaeeli M et al. G(-) anaerobes-reactive CD4+ T-cells trigger RANKL-mediated enhanced alveolar bone loss in diabetic NOD mice. Diabetes54, 1477–1486 (2005).
   PubMed Web of Science ®Google Scholar
• Zhang J, Fu M, Myles D et al. PDGF induces osteoprotegerin expression in vascular smooth muscle cells by multiple signal pathways. FEBS Lett.521, 180–184 (2002).
   PubMed Web of Science ®Google Scholar
• Fu M, Zhang J, Lin Y, Zhu X, Willson T, Chen Y. Activation of peroxisome proliferator-activated receptor inhibits osteoprotegerin gene expression in human aortic smooth muscle cells. Biochem. Biophys. Res. Commun.294, 597–601 (2002).
   PubMedGoogle Scholar
• Mosheimer BA, Kaneider NC, Feistritzer C et al. Syndecan-1 is involved in osteoprotegerin-induced chemotaxis in human peripheral blood monocytes. J. Clin. Endocrinol. Metab.90, 2964–2971 (2005).
   PubMedGoogle Scholar
• Malyankar UM, Scatena M, Suchland KL, Yun TJ, Clark EA, Giachelli CM. Osteoprotegerin is an α vβ 3-induced, NF-κ B-dependent survival factor for endothelial cells. J. Biol. Chem.275, 20959–20962 (2000).
   PubMed Web of Science ®Google Scholar
• Bennet MR. Apoptosis in the cardiovascular system. Heart87, 480–487 (2002).
   PubMedGoogle Scholar
• Tabas I. Consequences and therapeutic implications of macrophage apoptosis in atherosclerosis: the importance of lesion stage and phagocytic efficiency. Arterioscler. Thromb. Vasc. Biol.25, 2255–2264 (2005).
   PubMed Web of Science ®Google Scholar
• Jono S, Ikari Y, Shioi A et al. Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease. Circulation106, 1192–1194 (2002).
   PubMed Web of Science ®Google Scholar
• Avignon A, Sultan A, Piot C, Elaerts S, Cristol JP, Dupuy AM. Osteoprotegerin is associated with silent coronary artery disease in high-risk but asymptomatic type 2 diabetic patients. Diabetes Care28, 2176–2180 (2005).
   PubMed Web of Science ®Google Scholar
• Ziegler S, Kudlacek S, Luger A, Minar E. Osteoprotegerin plasma concentrations correlate with severity of peripheral artery disease. Atherosclerosis182, 175–180 (2005).
   PubMed Web of Science ®Google Scholar
• Morena M, Terrier N, Jaussent I et al. Plasma osteoprotegerin is associated with mortality in hemodialysis patients. J. Am. Soc. Nephrol.17, 262–270 (2006).
   PubMed Web of Science ®Google Scholar
• Kees M, Wiesbauer F, Gisslinger B, Wagner R, Shehata M, Gisslinger H. Elevated plasma osteoprotegerin levels are associated with venous thrombosis and bleeding in patients with polycythemia vera. Thromb. Haemost.93, 70–75 (2005).
   PubMedGoogle Scholar
• Brandstrom H, Stiger F, Kahan T et al. A single nucleotide polymorphism in the promoter region of the osteoprotegerin gene is related to intima-media thickness of the carotid artery in hypertensive patients. The Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA). Blood Press.13, 152–157 (2004).
   PubMed Web of Science ®Google Scholar
• Soufi M, Schoppet M, Sattler A et al. Osteoprotegerin gene polymorphisms in men with coronary artery disease. J. Clin. Endocrinol. Metab.89, 3764–3768 (2004).
   PubMed Web of Science ®Google Scholar
• Schoppet M, Schaefer JR, Hofbauer LC. Low serum levels of soluble RANK ligand are associated with the presence of coronary artery disease in men. Circulation107, E76 (2003).
   PubMedGoogle Scholar
• Hofbauer LC, Shui C, Riggs BL et al. Effects of immunosuppressants on receptor activator of NF-κB ligand and osteoprotegerin production by human osteoblastic and coronary artery smooth muscle cells. Biochem. Biophys. Res. Commun.280, 334–339 (2001).
   PubMed Web of Science ®Google Scholar
• Fahrleitner A, Prenner G, Leb G et al. Serum osteoprotegerin is a major determinant of bone density development and prevalent vertebral fracture status following cardiac transplantation. Bone32, 96–106 (2002).
   Google Scholar
• Sato T, Tominaga Y, Iwasaki Y et al. Osteoprotegerin levels before and after renal transplantation. Am. J. Kidney Dis.38, 175–177 (2001).
   PubMedGoogle Scholar
• Sasaki N, Kusano E, Ando Y et al. Changes in osteoprotegerin and markers of bone metabolism during glucocorticoid treatment in patients with chronic glomerulonephritis. Bone30, 853–858 (2002).
   PubMed Web of Science ®Google Scholar
• Viereck V, Grundker C, Blaschke S et al. Atorvastatin stimulates the production of osteoprotegerin by human osteoblasts. J. Cell. Biochem.96, 1244–1253 (2005).
   PubMedGoogle Scholar
• Kaji H, Kanatani M, Sugimoto T, Chihara K. Statins modulate the levels of osteoprotegerin/receptor activator of NFκB ligand mRNA in mouse bone-cell cultures. Horm. Metab. Res.37, 589–592 (2005).
   PubMed Web of Science ®Google Scholar
• McClung MR, Lewiecki EM, Cohen SB et al. AMG 162 Bone Loss Study Group. Denosumab in postmenopausal women with low bone mineral density. N. Engl. J. Med.354, 821–831 (2006).
   PubMed Web of Science ®Google Scholar
• Bekker PJ, Holloway DL, Rasmussen AS et al. A single-dose placebo-controlled study of AMG 162, a fully human monoclonal antibody to RANKL, in postmenopausal women. J. Bone Miner. Res.19, 1059–1066 (2004).
   PubMed Web of Science ®Google Scholar
• Bekker PJ, Holloway D, Nakanishi A, Arrighi M, Leese PT, Dunstan CR. The effect of a single dose of osteoprotegerin in postmenopausal women. J. Bone Miner. Res.16, 348–360 (2001).
   PubMed Web of Science ®Google Scholar
• Whyte MP. The long and the short of bone therapy. N. Engl. J. Med.354, 860–863 (2006).
   PubMed Web of Science ®Google Scholar