Vascular calcification in chronic kidney disease: are biomarkers useful for probing the pathobiology and the health risks of this process in the clinical scenario?

Patients with chronic kidney disease (CKD) are at a particularly high risk for cardiovascular disease. Vascular calcification (VC) is considered a cardiovascular risk marker, so in CKD patients screening for the presence of VC is suggested in current guidelines. VC is the result of both passive and active processes that involve a variety of proteins and factors. In the CKD population, numerous studies have identified circulating biomarkers potentially responsible for VC and have evaluated their link with this process. This narrative review, and an accompanying analysis performed on the Amiens CKD database, focuses on selected VC biomarkers-namely phosphate, fibroblast growth factor 23 (FGF23), osteopontin (OPN), osteoprotegerin (OPG), matrix Gla protein and fetuin A-all of which have been implicated as major players in VC in experimental studies in vitro or in animal models. None of the VC biomarkers considered in this review have qualified as a reliable predictor of meaningful clinical events or as a valid indicator of the risk of having VC. In the analysis based on the Amiens-CKD database, no biomarker outperformed age and the classical risk factors as a predictor of VC either in the aorta or in the coronaries. Well-designed clinical trials are now urgently needed to test the potential value of these biomarkers as a guide for interventions targeting VC.

[1]  W. van Biesen,et al.  Glucose-lowering drugs in patients with chronic kidney disease: a narrative review on pharmacokinetic properties. , 2014, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[2]  Huiliang Xie,et al.  Effects of dietary phosphate restriction and phosphate binders on FGF23 levels in CKD. , 2013, Clinical journal of the American Society of Nephrology : CJASN.

[3]  M. Budoff,et al.  Fibroblast growth factor 23 is not associated with and does not induce arterial calcification , 2013, Kidney international.

[4]  Z. Massy,et al.  Magnesium prevents phosphate-induced calcification in human aortic vascular smooth muscle cells , 2012, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[5]  D. Fliser,et al.  Plasma Klotho is not related to kidney function and does not predict adverse outcome in patients with chronic kidney disease. , 2013, Kidney international.

[6]  Z. Massy,et al.  Circulating Klotho levels: clinical relevance and relationship with tissue Klotho expression. , 2013, Kidney international.

[7]  J. Floege,et al.  Nanoparticle-based test measures overall propensity for calcification in serum. , 2012, Journal of the American Society of Nephrology : JASN.

[8]  B. Kestenbaum,et al.  Effects of phosphate binders in moderate CKD. , 2012, Journal of the American Society of Nephrology : JASN.

[9]  W. Richards,et al.  FGF23 neutralization improves chronic kidney disease-associated hyperparathyroidism yet increases mortality. , 2012, The Journal of clinical investigation.

[10]  M. Kuro-o,et al.  The emerging role of Klotho in clinical nephrology. , 2012, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[11]  Y. Caliskan,et al.  Osteoprotegerin/RANKL axis and progression of coronary artery calcification in hemodialysis patients. , 2012, Clinical journal of the American Society of Nephrology : CJASN.

[12]  I. Jaussent,et al.  Bone Biomarkers Help Grading Severity of Coronary Calcifications in Non Dialysis Chronic Kidney Disease Patients , 2012, PloS one.

[13]  L. Hsiao,et al.  Vascular Klotho Deficiency Potentiates the Development of Human Artery Calcification and Mediates Resistance to Fibroblast Growth Factor 23 , 2012, Circulation.

[14]  A. Bellasi,et al.  Mortality in kidney disease patients treated with phosphate binders: a randomized study. , 2012, Clinical journal of the American Society of Nephrology : CJASN.

[15]  L. Hofbauer,et al.  Serum level of the phosphaturic factor FGF23 is associated with abdominal aortic calcification in men: the STRAMBO study. , 2012, The Journal of clinical endocrinology and metabolism.

[16]  L. Schurgers,et al.  Effect of vitamin K2 supplementation on functional vitamin K deficiency in hemodialysis patients: a randomized trial. , 2012, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[17]  Z. Massy,et al.  Lanthanum carbonate, like sevelamer-HCl, retards the progression of vascular calcification and atherosclerosis in uremic apolipoprotein E-deficient mice. , 2012, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[18]  R. Strieter,et al.  Phosphate Binders in CKD: Bad News or Good News? , 2012 .

[19]  Z. Massy,et al.  FGF23 is independently associated with vascular calcification but not bone mineral density in patients at various CKD stages , 2012, Osteoporosis International.

[20]  Jeffrey A. White,et al.  Daily peritoneal administration of sodium pyrophosphate in a dialysis solution prevents the development of vascular calcification in a mouse model of uraemia. , 2011, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[21]  B. Kestenbaum,et al.  Association of serum phosphate levels with aortic valve sclerosis and annular calcification: the cardiovascular health study. , 2011, Journal of the American College of Cardiology.

[22]  M. Sánchez-Niño,et al.  The inflammatory cytokines TWEAK and TNFα reduce renal klotho expression through NFκB. , 2011, Journal of the American Society of Nephrology : JASN.

[23]  Jiang He,et al.  Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. , 2011, JAMA.

[24]  H. Jung,et al.  Fetuin-A, coronary artery calcification and outcome in maintenance hemodialysis patients. , 2011, Clinical nephrology.

[25]  S. Nasr,et al.  Proliferative glomerulonephritis secondary to dysfunction of the alternative pathway of complement. , 2011, Clinical journal of the American Society of Nephrology : CJASN.

[26]  H. Mischak,et al.  Markers of vascular disease in plasma from patients with chronic kidney disease identified by proteomic analysis , 2011, Journal of hypertension.

[27]  Z. Massy,et al.  Tumor Necrosis Factor‐Related Apoptosis‐Inducing Ligand and Vascular Calcification , 2011, Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy.

[28]  A. Hayen,et al.  Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease: a systematic review and meta-analysis. , 2011, JAMA.

[29]  N. Hirawa,et al.  Effect of sevelamer and calcium-based phosphate binders on coronary artery calcification and accumulation of circulating advanced glycation end products in hemodialysis patients. , 2011, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[30]  W. C. O'Neill,et al.  Treatment with pyrophosphate inhibits uremic vascular calcification. , 2011, Kidney international.

[31]  K. Polkinghorne,et al.  Attenuation of aortic calcification with lanthanum carbonate versus calcium‐based phosphate binders in haemodialysis: A pilot randomized controlled trial , 2011, Nephrology.

[32]  J. Craig,et al.  Phosphate binders for preventing and treating bone disease in chronic kidney disease patients. , 2011, The Cochrane database of systematic reviews.

[33]  L. Schurgers,et al.  Circulating nonphosphorylated carboxylated matrix gla protein predicts survival in ESRD. , 2011, Journal of the American Society of Nephrology : JASN.

[34]  D. Zwolińska,et al.  Vascular Calcification in Chronic Kidney Disease , 2008 .

[35]  K. Nitta,et al.  Serum fibroblast growth factor-23 levels and progression of aortic arch calcification in non-diabetic patients on chronic hemodialysis. , 2011, Journal of atherosclerosis and thrombosis.

[36]  A. El-shehaby,et al.  Association of fetuin-A and cardiac calcification and inflammation levels in hemodialysis patients , 2010, Scandinavian journal of clinical and laboratory investigation.

[37]  Z. Massy,et al.  Prognostic Implication of Plasma Osteopontin Levels in Patients with Chronic Kidney Disease , 2010, Nephron Clinical Practice.

[38]  Takayuki Hamano,et al.  Fetuin-mineral complex reflects extraosseous calcification stress in CKD. , 2010, Journal of the American Society of Nephrology : JASN.

[39]  Y. Ikari,et al.  Fetuin-A is associated with calcified coronary artery disease , 2010, Coronary artery disease.

[40]  Usama A A Sharaf El Din,et al.  Fibroblast growth factor-23 (FGF-23) is independently correlated to aortic calcification in haemodialysis patients. , 2010, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[41]  F. Turgut,et al.  Vascular calcification in chronic kidney disease. , 2010, Clinical science.

[42]  S. Goldstein,et al.  Malnutrition‐inflammation‐coronary calcification in pediatric patients receiving chronic hemodialysis , 2010, Hemodialysis international. International Symposium on Home Hemodialysis.

[43]  M. Wolf,et al.  Recent advances in the rapidly evolving field of fibroblast growth factor 23 in chronic kidney disease , 2010, Current opinion in nephrology and hypertension.

[44]  H. Koyama,et al.  Fetuin-A and atherosclerotic calcified plaque in patients with type 2 diabetes mellitus. , 2010, Metabolism: clinical and experimental.

[45]  L. Schurgers,et al.  The association of uncarboxylated matrix Gla protein with mitral annular calcification differs by diabetes status: The Heart and Soul study. , 2010, Atherosclerosis.

[46]  D. Besselsen,et al.  Tumor necrosis factor and interferon-gamma down-regulate Klotho in mice with colitis. , 2010, Gastroenterology.

[47]  L. Schurgers,et al.  The circulating inactive form of matrix gla protein is a surrogate marker for vascular calcification in chronic kidney disease: a preliminary report. , 2010, Clinical journal of the American Society of Nephrology : CJASN.

[48]  J. Waarsing,et al.  Dietary magnesium, not calcium, prevents vascular calcification in a mouse model for pseudoxanthoma elasticum , 2010, Journal of molecular medicine.

[49]  V. Jorgetti,et al.  Early control of PTH and FGF23 in normophosphatemic CKD patients: a new target in CKD-MBD therapy? , 2010, Clinical journal of the American Society of Nephrology : CJASN.

[50]  P. Galan,et al.  Pulse wave velocity and vascular calcification at different stages of chronic kidney disease , 2010, Journal of hypertension.

[51]  HalaAbdel-Hameed Abdel-Azeez,et al.  Plasma osteopontin as a predictor of coronary artery disease: association with echocardiographic characteristics of atherosclerosis , 2010, Journal of clinical laboratory analysis.

[52]  W. C. O'Neill,et al.  Plasma pyrophosphate and vascular calcification in chronic kidney disease. , 2010, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[53]  Won-Young Lee,et al.  The relationship between coronary artery calcification score, plasma osteoprotegerin level and arterial stiffness in asymptomatic type 2 DM , 2010, Acta Diabetologica.

[54]  K. Chinnaiyan,et al.  Annual progression of coronary calcification in trials of preventive therapies: a systematic review. , 2009, Archives of internal medicine.

[55]  I. Jaussent,et al.  A cut-off value of plasma osteoprotegerin level may predict the presence of coronary artery calcifications in chronic kidney disease patients. , 2009, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[56]  D. Spiegel,et al.  Long‐term effects of magnesium carbonate on coronary artery calcification and bone mineral density in hemodialysis patients: A pilot study , 2009, Hemodialysis international. International Symposium on Home Hemodialysis.

[57]  Liang-ying Gan,et al.  Relationship of sRANKL Level and Vascular Calcification Score to Cardiovascular Events in Maintenance Hemodialysis Patients , 2009, Blood Purification.

[58]  A. Macleod,et al.  Clinical Practice Guideline for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease- Mineral and Bone Disorder (CKD-MBD) , 2009 .

[59]  S. Booth,et al.  Vitamin K supplementation and progression of coronary artery calcium in older men and women. , 2009, The American journal of clinical nutrition.

[60]  M. D. de Broe,et al.  Adequate phosphate binding with lanthanum carbonate attenuates arterial calcification in chronic renal failure rats. , 2009, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[61]  Thomas J. Wang,et al.  Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Chronic Kidney Disease , 2009, Circulation.

[62]  N. Ozer,et al.  Association of plasma osteopontin levels with coronary calcification evaluated by tomographic coronary calcium scoring , 2009, Journal of Bone and Mineral Metabolism.

[63]  A. Mahnken,et al.  Relation of circulating matrix Gla-protein and anticoagulation status in patients with aortic valve calcification , 2009, Thrombosis and Haemostasis.

[64]  B. Kestenbaum,et al.  Association of serum phosphate with vascular and valvular calcification in moderate CKD. , 2009, Journal of the American Society of Nephrology : JASN.

[65]  J. V. van Engelshoven,et al.  Vascular calcifications as a marker of increased cardiovascular risk: A meta-analysis , 2009, Vascular health and risk management.

[66]  A. Mahnken,et al.  Uncarboxylated matrix Gla protein (ucMGP) is associated with coronary artery calcification in haemodialysis patients , 2009, Thrombosis and Haemostasis.

[67]  C. Chazot,et al.  Peripheral vascular calcification in long-haemodialysis patients: associated factors and survival consequences. , 2008, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[68]  Supplemental Tables,et al.  KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). , 2009, Kidney international. Supplement.

[69]  L. Schurgers,et al.  Dialysis Accelerates Medial Vascular Calcification in Part by Triggering Smooth Muscle Cell Apoptosis , 2008, Circulation.

[70]  Yin Tintut,et al.  Vascular calcification: pathobiology of a multifaceted disease. , 2008, Circulation.

[71]  M. Matsuhisa,et al.  Serum Osteoprotegerin as a Screening Tool for Coronary Artery Calcification Score in Diabetic Pre-Dialysis Patients , 2008, Hypertension Research.

[72]  L. Schurgers,et al.  The Circulating Inactive Form of Matrix Gla Protein (ucMGP) as a Biomarker for Cardiovascular Calcification , 2008, Journal of Vascular Research.

[73]  A. Kastrati,et al.  Relation between plasma fibroblast growth factor‐23, serum fetuin‐A levels and coronary artery calcification evaluated by multislice computed tomography in patients with normal kidney function , 2008, Clinical endocrinology.

[74]  M. Inaba,et al.  Serum magnesium concentration is a significant predictor of mortality in maintenance hemodialysis patients. , 2007, Magnesium research.

[75]  W. Suki,et al.  Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients. , 2007, Kidney international.

[76]  M. Inaba,et al.  Significant association between the presence of peripheral vascular calcification and lower serum magnesium in hemodialysis patients. , 2007, Clinical nephrology.

[77]  L. Schurgers,et al.  Undercarboxylated Matrix GLA Protein Levels Are Decreased in Dialysis Patients and Related to Parameters of Calcium-Phosphate Metabolism and Aortic Augmentation Index , 2007, Blood Purification.

[78]  Jason R. Stubbs,et al.  PHOSPHORUS METABOLISM AND MANAGEMENT IN CHRONIC KIDNEY DISEASE: Role of Fibroblast Growth Factor 23 in Phosphate Homeostasis and Pathogenesis of Disordered Mineral Metabolism in Chronic Kidney Disease , 2007, Seminars in dialysis.

[79]  M. Shlipak,et al.  Association of Fetuin-A With Mitral Annular Calcification and Aortic Stenosis Among Persons With Coronary Heart Disease: Data From the Heart and Soul Study , 2007, Circulation.

[80]  R. D'Agostino,et al.  Relations of serum phosphorus and calcium levels to the incidence of cardiovascular disease in the community. , 2007, Archives of internal medicine.

[81]  A. Khera,et al.  Relation of osteoprotegerin to coronary calcium and aortic plaque (from the Dallas Heart Study). , 2007, The American journal of cardiology.

[82]  M. Padrines,et al.  Key roles of the OPG–RANK–RANKL system in bone oncology , 2007, Expert review of anticancer therapy.

[83]  N. Chen,et al.  Fetuin-A uptake in bovine vascular smooth muscle cells is calcium dependent and mediated by annexins. , 2007, American journal of physiology. Renal physiology.

[84]  P. Raggi,et al.  Clinical assessment of vascular calcification. , 2007, Advances in chronic kidney disease.

[85]  D. Kiel,et al.  Matrix Gla Protein Is Associated With Risk Factors for Atherosclerosis but not With Coronary Artery Calcification , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[86]  M. Inaba,et al.  Role of fibroblast growth factor-23 in peripheral vascular calcification in non-diabetic and diabetic hemodialysis patients , 2006, Osteoporosis International.

[87]  Hang Lee,et al.  Regulation of C‐Terminal and Intact FGF‐23 by Dietary Phosphate in Men and Women , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[88]  A. Lahiri,et al.  The relationship between plasma osteoprotegerin levels and coronary artery calcification in uncomplicated type 2 diabetic subjects. , 2006, Journal of the American College of Cardiology.

[89]  Z. Massy,et al.  Sevelamer Prevents Uremia-Enhanced Atherosclerosis Progression in Apolipoprotein E–Deficient Mice , 2005, Circulation.

[90]  J. Skepper,et al.  Multifunctional roles for serum protein fetuin-a in inhibition of human vascular smooth muscle cell calcification. , 2005, Journal of the American Society of Nephrology : JASN.

[91]  W. C. O'Neill,et al.  Reduced plasma pyrophosphate levels in hemodialysis patients. , 2005, Journal of the American Society of Nephrology : JASN.

[92]  J. Woo,et al.  Associations of serum fetuin-A with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients. , 2005, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[93]  C. Reutelingsperger,et al.  Novel Conformation-Specific Antibodies Against Matrix γ-Carboxyglutamic Acid (Gla) Protein: Undercarboxylated Matrix Gla Protein as Marker for Vascular Calcification , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[94]  M. Budoff,et al.  Serum fetuin-A in nondialyzed patients with diabetic nephropathy: relationship with coronary artery calcification. , 2005, Kidney international.

[95]  B. Kestenbaum,et al.  Serum phosphate levels and mortality risk among people with chronic kidney disease. , 2005, Journal of the American Society of Nephrology : JASN.

[96]  L. Schurgers,et al.  Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations: a potential mechanism for accelerated vascular calcification in ESRD. , 2004, Journal of the American Society of Nephrology : JASN.

[97]  JonathanGolledge,et al.  Osteoprotegerin and Osteopontin Are Expressed at High Concentrations Within Symptomatic Carotid Atherosclerosis , 2004 .

[98]  K. Nitta,et al.  Serum osteoprotegerin levels and the extent of vascular calcification in haemodialysis patients. , 2004, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[99]  I. Tzanakis,et al.  Intra- and extracellular magnesium levels and atheromatosis in haemodialysis patients. , 2004, Magnesium research.

[100]  S. Saito,et al.  Matrix Gla protein is associated with coronary artery calcification as assessed by electron-beam computed tomography , 2004, Thrombosis and Haemostasis.

[101]  Reiko Ohmori,et al.  Plasma osteopontin levels are associated with the presence and extent of coronary artery disease. , 2003, Atherosclerosis.

[102]  A. Schwarz,et al.  The serum protein α2–Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification , 2003 .

[103]  C. Wanner,et al.  Deficiencies of calcium-regulatory proteins in dialysis patients: a novel concept of cardiovascular calcification in uremia. , 2003, Kidney international. Supplement.

[104]  C. Wanner,et al.  Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: a cross-sectional study , 2003, The Lancet.

[105]  P. Brunner,et al.  Media calcification, low erythrocyte magnesium, altered plasma magnesium, and calcium homeostasis following grafting of the thoracic aorta to the infrarenal aorta in the rat--differential preventive effects of long-term oral magnesium supplementation alone and in combination with alkali. , 2003, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[106]  M. McKee,et al.  Osteopontin inhibits mineral deposition and promotes regression of ectopic calcification. , 2002, The American journal of pathology.

[107]  Sharon M Moe,et al.  Phosphorus and uremic serum up-regulate osteopontin expression in vascular smooth muscle cells. , 2002, Kidney international.

[108]  Y. Ikari,et al.  Serum Osteoprotegerin Levels Are Associated With the Presence and Severity of Coronary Artery Disease , 2002, Circulation.

[109]  P. Raggi,et al.  Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. , 2002, Kidney international.

[110]  K. Boström,et al.  Matrix GLA Protein, a Regulatory Protein for Bone Morphogenetic Protein-2* , 2002, The Journal of Biological Chemistry.

[111]  K. Nitta,et al.  Soluble Osteopontin and Vascular Calcification in Hemodialysis Patients , 2001, Nephron.

[112]  M. McKee,et al.  Phosphate regulation of vascular smooth muscle cell calcification. , 2000, Circulation research.

[113]  C. Giachelli,et al.  Phosphorylation of Osteopontin Is Required for Inhibition of Vascular Smooth Muscle Cell Calcification* , 2000, The Journal of Biological Chemistry.

[114]  Sundeep Khosla,et al.  The Roles of Osteoprotegerin and Osteoprotegerin Ligand in the Paracrine Regulation of Bone Resorption , 2000, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[115]  A. Beynen,et al.  The influence of dietary phosphorus and magnesium concentrations on the calcium content of heart and kidneys of DBA/2 and NMRI mice , 1998, Laboratory animals.

[116]  Sílvia Ribeiro,et al.  Cardiac valve calcification in haemodialysis patients: role of calcium-phosphate metabolism. , 1998, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[117]  J. Skepper,et al.  Calcification of human vascular cells in vitro is correlated with high levels of matrix Gla protein and low levels of osteopontin expression. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[118]  Tadashi Kaname,et al.  Mutation of the mouse klotho gene leads to a syndrome resembling ageing , 1997, Nature.

[119]  I. Tzanakis,et al.  Mitral annular calcifications in haemodialysis patients: a possible protective role of magnesium. , 1997, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[120]  G Shimamoto,et al.  Osteoprotegerin: A Novel Secreted Protein Involved in the Regulation of Bone Density , 1997, Cell.

[121]  R. Behringer,et al.  Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein , 1997, Nature.

[122]  S. Schwartz,et al.  Osteopontin is synthesized by macrophage, smooth muscle, and endothelial cells in primary and restenotic human coronary atherosclerotic plaques. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[123]  W. Edwards,et al.  Diffuse calcification in human coronary arteries. Association of osteopontin with atherosclerosis. , 1994, The Journal of clinical investigation.

[124]  D. Denhardt,et al.  Osteopontin: a protein with diverse functions , 1993, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[125]  K. Hirokawa,et al.  Osteopontin mRNA is expressed by smooth muscle-derived foam cells in human atherosclerotic lesions of the aorta. , 1993, The Journal of clinical investigation.

[126]  P. Price,et al.  1,25-Dihydroxyvitamin D3 stimulates the synthesis of matrix gamma-carboxyglutamic acid protein by osteosarcoma cells. Mutually exclusive expression of vitamin K-dependent bone proteins by clonal osteoblastic cell lines. , 1988, The Journal of biological chemistry.

[127]  D. Heinegård,et al.  Cloning and sequence analysis of rat bone sialoprotein (osteopontin) cDNA reveals an Arg-Gly-Asp cell-binding sequence. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[128]  J. Meyer,et al.  Can biological calcification occur in the presence of pyrophosphate? , 1984, Archives of biochemistry and biophysics.

[129]  M. Urist,et al.  Matrix Gla protein, a new gamma-carboxyglutamic acid-containing protein which is associated with the organic matrix of bone. , 1983, Biochemical and biophysical research communications.

[130]  R. Bennett,et al.  Factors affecting the solubility of calcium pyrophosphate dihydrate crystals. , 1975, The Journal of clinical investigation.