Bone morphogenetic proteins in vascular calcification

Circulation Research

Volumn 97, Issue 2, 2005, Pages 105-114

  Hruska, Keith A ^a,b   Mathew, Suresh ^a   Saab, Georges ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b McDonnell Pediatric Research Building ^*  (United States)

Author keywords

Bone morphogenetic proteins; Chronic kidney disease; MSX 2; Smad6; Vascular calcification; Vascular smooth muscle cells

Indexed keywords

BONE MORPHOGENETIC PROTEIN; BONE MORPHOGENETIC PROTEIN 2; OSTEOCALCIN; OSTEOGENIC PROTEIN 1; SMAD6 PROTEIN;

ANIMAL CELL; APOPTOSIS; BLOOD VESSEL CALCIFICATION; BONE REMODELING; CELL DIFFERENTIATION; CHRONIC KIDNEY DISEASE; EXTRACELLULAR MATRIX; MINERALIZATION; MOUSE; NONHUMAN; PHOSPHATE BLOOD LEVEL; PRIORITY JOURNAL; PROTEIN FAMILY; PROTEIN LOCALIZATION; REVIEW; TUNICA MEDIA; VASCULAR SMOOTH MUSCLE;

ANIMALS; APOPTOSIS; BONE DEVELOPMENT; BONE MORPHOGENETIC PROTEINS; CALCINOSIS; CHRONIC DISEASE; DNA-BINDING PROTEINS; HOMEODOMAIN PROTEINS; HUMANS; KIDNEY DISEASES; MUSCLE, SMOOTH, VASCULAR; NEOPLASM PROTEINS; OSTEOBLASTS; PHENOTYPE; PHOSPHATES; RECEPTORS, LDL; TRANSCRIPTION FACTORS; VASCULAR DISEASES;

EID: 22744434737     PISSN: 00097330     EISSN: None     Source Type: Journal    
DOI: 10.1161/01.RES.00000175571.53833.6c     Document Type: Review

References (105)

1. Davies MR, Hruska KA. Pathophysiological mechanisms of vascular calcification in end-stage renal disease. Kidney Int. 2001;60:472-479.
2. Towler DA, Bidder M, Latifi T, Coleman T, Semenkovich CF. Diet-induced diabetes activates an osteogenic gene regulatory program in the aortas of low density lipoprotein receptor-deficient mice. J Biol Chem. 1998;273:30427-30434.
3. Tyson KL, Reynolds JL, McNair R, Zhang Q, Weissberg PL, Shanahan CM. Osteo/chondrocytic transcription factors and their target genes exhibit distinct patterns of expression in human arterial calcification. Arterioscler Thromb Vasc Biol. 2003;23:489-494.
4. Proudfoot D, Skepper JN, Shanahan CM, Weissberg PL. Calcification of human vascular cells in vitro is correlated with high levels of matrix Gla protein and low levels of osteopontin expression. Arterioscler Thromb Vasc Biol. 1998;18:379-388.
5. Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao Y-H, lnada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. 1997;89:755-764.
6. Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, De Crombrugghe B. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 2002;108:17-29.
7. Satokata I, Ma L, Ohshima H, Bei M, Woo I, Nishizawa K, Maeda T, Takano Y, Uchiyama M, Heaney S, Peters H, Tang Z, Maxson R, Maas R. Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation. Nat Genet. 2004;24:391-395.
8. Mori-Akiyama Y, Akiyama H, Rowitch DH, deCrombrugghe B. Sox9 is required for determination of the chondrogenic cell lineage in the cranial neural crest. Proc Natl Acad Sci USA. 2003;100:9360-9365.
9. Karaplis, AC. Embryonic development of bone and the molecular regulation of intramembranous and endochondral bone formation. In: Bilezikian JP, Raisz LG, Rodan GA, eds. Principles of Bone Biology. San Diego: Academic Press;2002:33-58.
10. Vattikuti R, Towler DA. Osteogenic regulation of vascular calcification: an early perspective. Am J Physiol Endocriol Metab. 2004;286:E686-E696.
11. Boström K, Watson KE, Horn S, Worthman C, Herman M, Demer LL. Bone morphogenetic protein expression in human atherosclerotic lesions. J Clin Invest. 1993;91:1800-1809.
12. Reynolds JL, Joannides AJ, Skepper JN, McNair R, Schurgers LJ, Proudfoot D, Jahnen-Dechent W, Weissberg PL, Shanahan CM. 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. J Am Soc Nephrol. 2004;15:2857-2867.
13. Yang H, Curinga G, Giachelli CM. Elevated extracellular calcium levels induce smooth muscle cell matrix mineralization in vitro. Kidney Int. 2004; 66:2293-2299.
14. Mathew S, Tustison KS, Hruska KA. Bone morphogenetic protein-7 (BMP-7) restores human aortic vascular smooth muscle cell (HAoSMC) phenotype and inhibits calcification in vitro. J Am Soc Neph. 2004;15:7A.
15. Tintut Y, Alfonso Z, Saini T, Radcliff K, Watson K, Boström K, Demer LL. Multilineage potential of cells from the artery wall. Circulation. 2003;108: 2505-2510.
16. Kuwana M, Okazaki Y, Kodama H, Izumi K, Yasuoka H, Ogawa Y, Kawakami Y, Ikeda Y. Human circulating CD14+ monocytes as a source of progenitors that exhibit mesenchymal cell differentiation. J Leukoc Biol. 2003;74:833-845.
17. Doherty MJ, Ashton BA, Walsh S, Beresford JN, Grant ME, Canfield AE. Vascular pericytes express osteogenic potential in vitro and in vivo. J Bone Miner Res. 1998;13:828-838.
18. Kato M, Patel MS, Levasseur R, Lobov I, Chang BHJ, Glass DA, II, Hartmann C, Li L, Hwang TH, Brayton CF, Lang RA, Karsenty G, Chan L. Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol. 2002;157:303-314.
19. Cheng H, Jiang W, Phillips FM, Haydon RC, Peng Y, Zhou L, Luu HH, An N, Breyer B, Vanichakarn P, Szatkowski JP, Park JY, He TC. Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J Bone and Joint Surg. 2003;85:1544-1552.
20. Little RD, Carulli JP, DelMastro RG, Dupuis J, Osbome M, Folz C, Manning SP,- Swain PM, Zhao S-C, Eustace B, Lappe MM, Spitzer L, Zweier S, Braunschweiger K, Benchekroun Y, Hu X, Adair R, Chee L, Fitzgerald MG, Tulig C, Caruso A, Tzellas N, Bawa A, Franklin B, McGuire S, Nogues X, Gong G, Allen KM, Anisowicz A, Morales AJ, Lomedico PT, Recker SM, Van Eerdewegh P, Recker RR, Johnson ML. A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am J Hum Genet. 2002;70:11-19.
21. Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP. High bone density due to a mutation in LDL-receptor-related protein 5. NEJM. 2002;346:1513-1521.
22. Balemans W, Ebeling M, Patel N, Van Hul E, Olson P, Dioszegi M, Lacza C, Wuyts W, Van Den Ende J, Willems P, Paes-Alves AF, Hill S, Bueno M, Ramos FJ, Tacconi P, Dikkers FG, Stratakis C, Lindpaintner K, Vickery B, Foemzler D, Van Hul W. Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST). Hum Mol Genet. 2001; 10:537-543.
23. Brunkow ME, Gardner JC, Van Ness J, Paeper BW, Kovacevich BR, Proll S, Skonier JE, Zhao L, Sabo PJ, Fu Y, Alisch RS, Gillett L, Colbert T, Tacconi P, Galas D, Hamersma H, Beighton P, Mulligan J. Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet 2001;968:577-589.
24. Harada S-I, Rodan GA. Control of osteoblast function and regulation of bone mass. Nature. 2003;423:349-355.
25. Massague J, Chen YG. Controlling TGF-beta signaling. Genes Dev. 2000; 14:627-644.
26. Massague J, Wotton D. Transcriptional control by the TGF-β/Smad signaling system. EMBO J. 2000;19:1745-1754.
27. Shi Y, Wang Y-F, Jayaraman I, Yang H, Massague J, Pavletich N. Crystal structure of a Smad MH1 domain bound to DNA: Insights on DNA-binding in TGF-β signalling. Cell. 1998;94:595-594.
28. Chen X, Weisberg E, Fridmacher V, Watanabe M, Naco G, Whitman M. Smad4 and FAST-1 in the assembly of Activin-responsive factor. Nature. 1997;389:85-89.
29. Labbé E, Silvestri C, Hoodless PA, Wrana JL, Attisano L. Smad2 and Smad3 positively and negatively regulate TGFβ-dependent transcription through the fork-head DNA-binding protein. Mol Cell. 1998;2:109-120.
30. Saijoh Y, Adachi H, Sakuma R, Yeo CY, Yashiro K, Watanabe M, Hashiguchi H, Mochida K, Ohishi S, Kawabata M, Miyazono K, Whitman M, Hamada H. Left-right assymetric expression of lefly2 and nodal is induced by a signaling pathway that includes the transcription factor FAST2. Mol Cell. 2000;5:35-47.
31. Hata A, Seoane J, Lagna G, Montalvo E, Hemmati-Brivanlou A, Massague J. OAZ uses distinct DNA- and protein-binding zinc fingers in separate BMP-Smad and Olf signaling pathways. Cell. 2000;100:229-240.
32. Germain S, Howell M, Esslemont GM, Hill CS. Homeodomain and winged-helix transcription factors recruit activated Smads to distinct promoter elements via a common Smad interaction motif. Genes Dev. 2000;14:435-451.
33. Piccolo S, Sasai Y, Lu B, De Robertis EM. Dorso-ventral patterning in Xenopus: Inhibition of ventral signals by direct inding of chordin to BMP-4. Cell. 1996;86:589-598.
34. Zimmerman LB, De Jesus-Escobar JM, Harland RM. The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4. Cell. 1996;86:599-606.
35. Stanley E, Biben C, Kotecha S, Fabri L, Tajbakhsh S, Wang CC, Hatzistavrou T, Roberts B, Drinkwater C, Lan M, et al. DAN is a secreted glycoprotein related to Xenopus cerberus. Mech Dev. 1998;88:173-184.
36. Pearce JJ, Penny G, Rossant J. A mouse cerberus/DAN-related gene family. Dev Biol. 1999;209:98-110.
37. Khokha MK, Hsu D, Brunet LJ, Dionne MS, Harland RM. Gremlin is the BMP antagonist required for maintenance of Shh and Fgf signals during limb patterning. Nat Genet. 2003;34:303-307.
38. Stanley E, Gilbert DG, Jenkins NA, Copeland NG, Harvey RP. Murine cerberus homologue Cerl maps to chromosome 4. Genomics. 1998;49: 337-338.
39. Simpson EH, Johnson DK, Hunsicker P, Suffolk R, Jordan SA, Jackson IJ. The mouse Cer1 (Cerberus related or homologue) gene is not required for anterior patttem formation. Dev Biol. 1999;213:202-206.
40. Piccolo S, Agius E, Leyns L, Bhattacharyya S, Grunz H, Bouwmeester T, De Robertis EM. The head inducer Cerberus is a multifunctional antagonist of Nodal, BMP and Wm signals. Nature. 1999;397:707-710.
41. Heldin C-H, Miyazono K, ten Dijke P. TGF-b signalling from cell membrane to nucleus through SMAD proteins. Nature. 1997;390:465-471.
42. Massague J. TGFβ signal transduction. Annu Rev Biochem. 1998;67: 758-791.
43. Souchelnytskyi S, Nakayama T, Nakao A, Morén A. Physical and functional interaction of murine and Xenopus Smad7 with bone morphogenetic protein receptors and transforming growth factor-β receptors. J Biol Chem. 1998;273:25364-25370.
44. Ishisaki A, Yamato K, Hashioto S, Nakao A, Tamaki K, Nonaka K, ten Dijke P, Sugino H, Nishihara T. Differential inhibition of Smad6 and Smad7 on bone morphogenetic protein- and Activin-mediated growth arrest and apoptosis in B cells. J Biol Chem. 1999;274:13637-13642.
45. Itoh S, Landstrom M, Hermansson A, Itoh F, Heldin CH, Heldin NE, ten Dijke P. Transforming growth factor betal induces nuclear export of inhibitory Smad7. J Biol Chem. 1998;273:29195-29201.
46. Galvin KM, Donovan MJ, Lynch CA, Meyer RI, Paul RJ, Lorenz JN, Fairchild-Huntress V, Dixon KL, Dunmore JH, Gimbrone MA Jr, Falb D, Huszar D. A role for Smad6 in development and homeostasis of the cardiovascular system. Nat Genet. 2000;24:171-174.
47. Rosen V, Wozney JM. Bone morphogenetic proteins. In: Bilezikian JP, Raisz LG, Rodan GA, eds. Principles of Bone Biology. San Diego: Academic Press; 1996:919-928.
48. Dhore CR, Cleutjens J, Lutgens E, Cleutjens K, Geussens P, Kitslaar P, Tordoir J, Spronk H, Vermeer C, Daemen M. Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques. Arterioscler Thromb Vasc Biol. 2001;21:1998-2003.
49. Griethe, W, Schmitt, R, Jurgensen, JS, Bachmann, S, Eckardt, K-U, Schindler, R. Bone morphogenic protein-4 expression in vascular lesions of calciphylaxis. J Nephrol. 2003;16:728-732.
50. Zhang H, Bradley A. Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Development. 1996; 122:2977-2986.
51. Spinella-Jaegle S, Roman-roman S, Faucheu C, Dunn FW, Kawai S, Gallea S, Stiot V, Blanchet AM, Courtois B, Baron R, Rawadi G. Opposite effects of bone morphogenetic protein-2 and transforming growth factor beta 1 on osteoblast differentiation. Bone. 2001;29:323-330.
52. Lee MH, Kim YJ, Kim HJ, Park HD, Kang AR, Kyung HM, Sung JH, Wozney JM, Kim HJ, Ryoo HM. BMP-2-induced Runx2 expression is mediated by Dlx5, and TGF-β1 opposes the BMP-2-induced osteoblast differentiation by suppression of Dlx5 expression. J Biol Chem. 2003;278: 34387-34394.
53. Chaudhary LR, Hofmeister AM, Hruska KA. Differential growth factor control of bone formation through osteoprogenitor differentiation. Bone. 2004;34:402-411.
54. Lee MH, Kwon TG, Park HS, Wozney JM, Ryoo HM. BMP-2-induced Osterix expression is mediated by Dlx5 but is independent of Runx2. Biochem Biophys Res Com. 2003;309:689-694.
55. Luo G, Hofmann C, Bronckers AL, Sohocki M, Bradley A, Karsenty G. BMP-7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning. Genes Dev. 1995;9:2808-2820.
56. Dudley AT, Robertson EJ. Overlapping expression domains of bone morphogenetic protein family members potentially account for limited tissue defects in BMP7 deficient embryos. Develop Dynamics. 1997;208: 349-362.
57. Vukicevic S, Kopp JB, Luyten FP, Sampath TK. Induction of nephrogenic mesenchyme by osteogenic protein 1 (bone morphogenetic protein 7). Proc Natl Acad Sci U S A. 1996;93:9021-9026.
58. Kitten AM, Kreisberg JI, Oison MS. Expression of osteogenic protein-1 mRNA in cultured kidney cells. J Cellular Physiol. 1999;181:410-415.
59. Simon M, Maresh JG, Harris SE, Hernandez JD, Arar M, Olson MS, Abboud HE. Expression of bone morphogenetic protein-7 mRNA in normal and ischemic adult rat kidney. Amer J Physiol. 1999;276:F382-F389.
60. Wang S, Chen Q, Simon TC, Strebeck F, Chaudhary L, Morrissey J, Liapis H, Klahr S, Hruska KA. Bone morphogenetic protein-7 (BMP-7), a novel therapy for diabetic nephropathy. Kidney Int. 2003;63:2037-2049.
61. Wang S, Hirschberg R. Loss of renal tubular BMP7 during the evolution of experimental diabetic nephropathy. J Am Soc Nephrol. 2000;11:655A.
62. Zohar R, McCulloch CA, Sampath K, Sodek J. Flow cytometric analysis of recombinant human osteogenic protein-1 (BMP-7) responsive subpopulations from fetal rat calvaria based on intracellular osteopontin content. Matrix Biol. 1998;16:295-306.
63. Asahina I, Sampath TK, Hauschka PV. Human osteogenic protein-1 induces chondroblastic, osteoblastic, and/or adipocytic differentiation of clonal murine target cells. Exp Cell Res. 1996;222:38-47.
64. Shea CM, Edgar CM, Einhorn TA, Gerstenfeld LC. BMP treatment of C3H10T1/2 mesenchymal stem cells induces both chondrogenesis and osteogenesis. J Cell Biochem. 2003;90:1112-1127.
65. Gerstenfeld LC, Cruceta J, Shea CM, Sampath K, Barnes GL, Einhorn TA. Chondrocytes provide morphogenic signals that selectively induce osteogenic differentiation of mesenchymal stem cells. J Bone Miner Res. 2002;17:221-230.
66. Hedin U, Roy J, Tran PK, Lundmark K, Rahman A. Control of smooth muscle cell proliferation - the role of the basement membrane. Thromb Haemost. 1999;82(Suppl.):23-26.
67. Wolf NF, Rolfe BE, Song J, Campbell R. Vascular smooth muscle cell phenotype modulation in culture is associated with reorganization of contractile and cytoskeletal proteins. Cell Motil Cytoskeleton. 2001;49: 130-145.
68. Thyberg J. Differentiated properties and proliferation of arterial smooth muscle cells in culture. Int Rev Cytol. 1996;169:183-265.
69. Schluesener HJ, Meyerman R. Immunolocalization of BMP-6, a novel TGF-β-related cytokine, in normal and atherosclerotic smooth muscle cells. Atherosclerosis. 1995;113:153-156.
70. Nakaoka T, Gonda K, Ogita T, Otawara-Hamamoto Y, Okabe F, Kira Y, Hari K, Miyazone K, Takuwah Y, Fujita T. Inhibition of rat vascular smooth muscle proliferation in vitro and in vivo by bone morphogenetic protein-2. J Clin Invest. 1997;100:2824-2832.
71. Wong GA, Tang V, El-Sabeawy F, Weiss RH. BMP-2 inhibits proliferation of human aortic smooth muscle cells via p21. Am J Physiol Endocriol Metab. 2003;284:E972-E979.
72. King KE, Iyemere VP, Weissberg PL, Shanahan CM. Kruppel-like factor 4 (KLF4/GKLF) is a target of bone morphogenetic proteins and transforming growth factor β1 in the regulation of vascular smooth muscle phenotype. J Biol Chem. 2003;278:11661-11669.
73. Cheng SL, Shao JS, Charlton-Kachigian N, Loewy AP, Towler DA. Msx2 promotes osteogenesis and suppresses adipogenic differentiation of multipotent mesenchymal progenitors. J Biol Chem. 2003;278:45969-45977.
74. Wilkie AOM, Tang Z, Elanko N, Walsh S, Twigg SRF, Hurst JA, Wall SA, Chrzanowska KH, Maxson RE, Jr. Functional haploinsufficiency of the human homeobox gene MSX2 causes defects in skull ossification. Nat Genet. 2004;24:387-390.
75. Hayashi Si, Morishita R, Matsushita H, Nakagami H, Taniyama Y, Nakamura T, Aoki M, Yamamoto K, Higaki J, Ogihara T. Cyclic AMP inhibited proliferation of human aortic vascular smooth muscle cells, accompanied by induction of p53 and p21. Hypertension. 2000;35:237-243.
76. Matsushita H, Morishita R, Kida R, Aoki M, Hayashi Si, Tomita N, Yamamoto K, Moriguchi A, Noda A, Kaneda Y, Higaki J, Ogihara T. Inhibition of growth of human vascular smooth muscle cells by overexpression of p21 gene through induction of apoptosis. Hypertension. 1998; 31:493-498.
77. Zhang S, Fantozzi I, Tigno DD, Yi ES, Platoshyn O, Thistlethwaite PA, Kriett JM, Yung G, Rubin LJ, Yuan JX. Bone morphogenetic proteins induce apoptosis in human pulmonary vascular smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2003;285:L740-L754.
78. Proudfoot D, Skepper JN, Hegyi L, Bennett MR, Shanahan CM, Weissberg PL. Apoptosis regulates human vascular calcification in vitro: evidence for initiation of vascular calcification by apoptotic bodies. Circ Res. 2000;87: 1055-1062.
79. Schoppet M, Al Fakhri N, Franke FE, Katz N, Barth PJ, Maisch B, Preissner KT, Hofbauer LC. Localization of osteoprotegerin, tumor necrosis factor-related apoptosis-inducing ligand, and receptor activator of nuclear factor-κB ligand in Monckeberg's sclerosis and atherosclerosis. J Clin Endocrinol Metab. 2004;89:4104-4112.
80. Parhami F, Morrow AD, Balucan J, Leitinger N, Watson AD, Tintut Y, Berliner JA, Demer LL. Lipid oxidaton products have opposite effects on calcifying vascular cell and bone cell differentiation: A possible explanation for the paradox of arterial calcifation in osteoporotic patients. Arterioscler Thromb Vasc Biol. 1997;17:680-687.
81. Fukui N, Zhu Y, Maloney WJ, Clohisy J, Sandell LJ. Stimulation of BMP-2 expression by pro-inflammatory cytokines IL-1 and TNF-α in normal and osteoarthritic chondrocytes. J Bone and Joint Surg. 2003;85:59-66.
82. Rifas L, Arackal S, Weitzmann MN. Inflammatory T cells rapidly induce differentiation of human bone marrow stromal cells into mature osteoblasts. J Cell Biochem. 2003;88:650-659.
83. Sirard C, Kim S, Mirtsos C, Tadich P, Hoodless PA, Itie A, Maxson R, Wrana JL, Mak TW. Targeted disruption in murine cells reveals variable requirement for Smad4 in transforming growth factor beta-related signaling. J Biol Chem. 2000;275:2063-2070.
84. Karsenty G. Minireview: Transcriptional control of osteoblast differentiation. Endocrinology. 2001;142:2731-2733.
85. Cohen MM Jr. Craniofacial disorders caused by mutations in homeobox genes MSX2 and. MSX2. J Craniofac Genetics and Develop Biol. 2000; 20:19-25.
86. Jabs EW, Muller U, Li X, Ma L, Luo W, Haworth IS, Klisak I, Sparkes R, Warman ML, Mulliken JB, Snead ML, Maxson R. A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis. Cell. 1993;75:443-450.
87. Ma L, Golden S, Wu L, Maxson R. The molecular basis of Boston-type craniosynostosis: the Pro148->His mutation in the N-terminal arm of the MSX2 homeodomain stabilizes DNA binding without altering nucleotide sequence preferences. Hum Mol Genet. 1996;5:1915-1920.
88. Zebboudj AF, Shin V, Boström K. Matrix GLA protein and BMP-2 regulate osteoinduction in calcifying vascular cells. J Cell Biochem. 2003;90: 756-765.
89. Boström K, Tsao D, Shen S, Wang Y, Demer LL. Matrix GLA protein modulates differentiation induced by bone morphogenetic protein-2 in C3H10T1/2 cells. J Biol Chem. 2001;276:14044-14052.
90. Luo G, Ducy P, McKee MD, Pinero GJ, Loyer E, Behringer RR, Karsenty G. Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature. 1997;386:78-81.
91. Shanahan CM, Cary NRB, 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. Circulation. 1999;100:2168-2176.
92. Hao H, Hirota S, Ishibashi-Ueda H, Kushiro T, Kanmatsuse K, Yulani C. Expression of matrix Gla protein and osteonectin mRNA by human aortic smooth muscle cells. Cardiovasc Pathol. 2004;13:195-202.
93. Dorai H, Vukicevic S, Sampath TK. Bone morphogenetic protein-7 (osteogenic protein-1) inhibits smooth muscle cell proliferation and stimulates the expression of markers that are characteristic of SMC phenotype in vitro. J Cellular Physiol. 2000:184:37-45.
94. Dorai H, Sampath TK. Bone morphogenetic protein-7 modulates genes that maintain the vascular smooth muscle cell phenotype in culture. J Bone and Joint Surg. 2001;83:S70-S78.
95. Barbara NP, Wrana JL, Letarte M. Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-beta superfamily. J Biol Chem. 1999;274: 584-594.
96. Piscione TD, Yager TD, Gupta IR, Grinfeld B, Pei Y, Attisano L, Wrana JL, Rosenblum ND. BMP-2 and OP-1 exert direct and opposite effects on renal branching morphogenesis. Am J Phys (Renal). 1997;273:F961-F975.
97. Piscione TD, Phan T, Rosenblum ND. BMP7 controls collecting tubule cell proliferation and apoptosis via Smad1-dependent and -independent pathways. Amer J Physiol. 2001;280:F19-F33.
98. 97a. Hruska KA, Saab G, Chaudhary LR, Quinn CO, Lund RJ, Surendran K. Kidney-bone, bone-kidney, and cell-cell communications in renal osteodystrophy. Semin Nephrol. 2004;24:25-38.
99. Davies MR, Lund RJ, Hruska KA. BMP-7 is an efficacious treatment of vascular calcification in a murine model of atherosclerosis and chronic renal failure. J Am Soc Neph. 2003;14:1559-1567.
100. Davies MR, Lund RJ, Mathew S, Hruska KA. Low turnover osteodystrophy and vascular calcification are amenable to skeletal anabolism in an animal model of chronic kidney disease and the metabolic syndrome. J Am Soc Neph. 2005;16:917-928.
101. Steitz SA, Speer MY, Curinga G, Yang H-Y, Haynes P, Aebersold R, Schinke T., Karsenty G, Giachelli CM. Smooth muscle cell phenotypic transition associated with calcification. Circ Res. 2001;89:1147-1154.
102. Jono S, Nishizawa Y, Shioi A, Mori H. Parathyroid hormone-related peptide as a local regulator of vascular calcification. Arterioscler Thromb Vasc Biol. 1997;17:1135-1142.
103. Jono S, McKee MD, Murry CE, Shioi A, Nishizawa Y, Mori K, Morii H, Giachelli CM. Phosphate regulation of vascular smooth muscle cell calcification. Circ Res. 2000;87:e10-e17.
104. Blacher J, Guerin AP, Pannier B, Marchais SJ, London GM. Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension. 2001;38:938-942.
105. Kurz P, Monier-Faugere M-C, Bognar B, Werner E, Roth P, Vlachojannis J, Malluche HH. Evidence for abnormal calcium homeostasis in patients with adynamic bone disease. Kidney Int. 1994;46:855-861.