2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2004100835v1 16/4/917    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Davies, M. R. Articles by Hruska, K. A. Search for Related Content PubMed PubMed Citation Articles by Davies, M. R. Articles by Hruska, K. A.

Low Turnover Osteodystrophy and Vascular Calcification Are Amenable to Skeletal Anabolism in an Animal Model of Chronic Kidney Disease and the Metabolic Syndrome

Matthew R. Davies^*, Richard. J. Lund^*, Suresh Mathew and Keith A. Hruska^*,,

^* Departments of Medicine, Pediatrics, and Cell Biology, Renal Divisions, Washington University School of Medicine, St. Louis, Missouri

Address correspondence to: Dr. Keith A. Hruska, Washington University School of Medicine, Campus Box 8208, 5th Floor MPRB, 660 S. Euclid Avenue, St. Louis, MO 63110. Phone: 314-286-2772; Fax: 314-286-2894; E-mail:hruska_k{at}wustl.edu

Received for publication October 8, 2004. Accepted for publication January 13, 2005.

LDL receptor (LDLR)–null mice fed high-fat/cholesterol diets, a model of the metabolic syndrome, have vascular calcification (VC) worsened by chronic kidney disease (CKD) and ameliorated by bone morphogenetic protein-7 (BMP-7), an efficacious agent in treating animal models of renal osteodystrophy. Here, LDLR–/– high-fat–fed mice without CKD were shown to have significant reductions in bone formation rates, associated with increased VC and hyperphosphatemia. Superimposing CKD resulted in a low turnover osteodystrophy, whereas VC worsened and hyperphosphatemia persisted. BMP-7 treatment corrected the hyperphosphatemia, corrected the osteodystrophy, and prevented VC, compatible with skeletal phosphate deposition leading to reduced plasma phosphate and removal of a major stimulus to VC. A pathologic link between abnormal bone mineralization and VC through the serum phosphorus was supported by the partial effectiveness of directly reducing the serum phosphate by a phosphate binder that had no skeletal action. Thus, in this model of the metabolic syndrome with CKD, a reduction in bone-forming potential of osteogenic cells leads to low bone turnover rates, producing hyperphosphatemia and VC, processes ameliorated by the skeletal anabolic agent BMP-7, in part through deposition of phosphate and increased bone formation.

This article has been cited by other articles:

				M. Pazianas, A. B. Rossebo, T. R. Pedersen, Y. A. Kesaniemi, and C. M. Otto Calcific Aortic Stenosis N. Engl. J. Med., January 1, 2009; 360(1): 85 - 86. [Full Text] [PDF]

				A. Jara, C. Chacon, M. E. Burgos, A. Droguett, A. Valdivieso, M. Ortiz, P. Troncoso, and S. Mezzano Expression of gremlin, a bone morphogenetic protein antagonist,is associated with vascular calcification in uraemia Nephrol. Dial. Transplant., November 21, 2008; (2008) gfn611v1. [Abstract] [Full Text] [PDF]

				S. Mathew, R. J. Lund, L. R. Chaudhary, T. Geurs, and K. A. Hruska Vitamin D Receptor Activators Can Protect against Vascular Calcification J. Am. Soc. Nephrol., August 1, 2008; 19(8): 1509 - 1519. [Abstract] [Full Text] [PDF]

				L. L. Demer and Y. Tintut Vascular Calcification: Pathobiology of a Multifaceted Disease Circulation, June 3, 2008; 117(22): 2938 - 2948. [Full Text] [PDF]

				V. M. Brandenburg and J. Floege Adynamic bone disease--bone and beyond NDT Plus, June 1, 2008; 1(3): 135 - 147. [Full Text] [PDF]

				S. Mathew, K. S. Tustison, T. Sugatani, L. R. Chaudhary, L. Rifas, and K. A. Hruska The Mechanism of Phosphorus as a Cardiovascular Risk Factor in CKD J. Am. Soc. Nephrol., June 1, 2008; 19(6): 1092 - 1105. [Abstract] [Full Text] [PDF]

				G. M. Mitu, S. Wang, and R. Hirschberg BMP7 is a podocyte survival factor and rescues podocytes from diabetic injury Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1641 - F1648. [Abstract] [Full Text] [PDF]

				H. Sugimoto, C. Yang, V. S. LeBleu, M. A. Soubasakos, M. Giraldo, M. Zeisberg, and R. Kalluri BMP-7 functions as a novel hormone to facilitate liver regeneration FASEB J, January 1, 2007; 21(1): 256 - 264. [Abstract] [Full Text] [PDF]

				S. Mathew, R. J. Lund, F. Strebeck, K. S. Tustison, T. Geurs, and K. A. Hruska Reversal of the Adynamic Bone Disorder and Decreased Vascular Calcification in Chronic Kidney Disease by Sevelamer Carbonate Therapy J. Am. Soc. Nephrol., January 1, 2007; 18(1): 122 - 130. [Abstract] [Full Text] [PDF]

				A. A. Eddy Ramping up endogenous defences against chronic kidney disease Nephrol. Dial. Transplant., May 1, 2006; 21(5): 1174 - 1177. [Full Text] [PDF]

				K. Olgaard and E. Lewin Can Hyperparathyroid Bone Disease Be Arrested or Reversed? Clin. J. Am. Soc. Nephrol., May 1, 2006; 1(3): 367 - 373. [Abstract] [Full Text] [PDF]

				M. Zeisberg Bone morphogenic protein-7 and the kidney: current concepts and open questions Nephrol. Dial. Transplant., March 1, 2006; 21(3): 568 - 573. [Full Text] [PDF]

				P Merkel, G. Lo, J. Holbrook, A. Tibbs, N. Allen, J. Davis, G. Hoffman, W. McCune, E. St Clair, U Specks, et al. Thromboembolism--Another Threat to the Polymorbid Patient with Vasculitis?: High Incidence of Venous Thrombotic Events among Patients with Wegener Granulomatosis: The Wegener's Clinical Occurrence of Thrombosis (WeCLOT) Study. Ann Intern Med 142: 620-626, 2005 J. Am. Soc. Nephrol., July 1, 2005; 16(7): 1871 - 1877. [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673