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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2011; 57(4): 96-112


Matrix Gla-protein and its role in vascular wall calcification

Harbuzova VIu, Ataman OV

    Sumy State University, Ukraine
DOI: https://doi.org/10.15407/fz57.04.096


Abstract

Data on the structure of matrix Gla-protein (MGP), its chemical characteristics, regulation of synthesis and post-translational modifications are described. The information on the structure of the MGP gene, its well distributed polymorphisms are presented. Factors that regulate expression and activity of MGP include vitamin D, retinoic acid, extracellular calcium ions, cytokines, and some hormones. It is emphasized that MGP is an important inhibitor of calcification of soft tissues. These properties of this protein are associated with the pres­ence of residues of g-carboxiglutamic acid of its molecule. Four possible mechanisms of anticalcinogenic action of MGP are described: binding with calcium ions and crystals of hydroxya-patite, binding to extracellular matrix components, interaction with bone morphogenetic protein (BMP-2) and elimination the effects of the latter, participation in the regulation of apoptosis. It is emphasized that the study of allelic variants of the MGP gene is important in the context of their possible association with the development of cardiovascular and other diseases.

Keywords: сосудистая стенка, кальцификация,полиморфизм генов, матриксный Gla-протеин.

References

  1. Baudet C., Perret E., Delpech B., Kaghad M., Brachet P., Wion D., Caput D. Differentially expressed genes in C6.9 glioma cells during vitamin D-induced cell death program . Cell Death Diff. 1998. 5. P. 116-125. CrossRef PubMed
  2.  
  3. Bobryshev Y. Calcification of elastic fibers in human atherosclerotic plaque . Atherosclerosis. 2005. 180. P. 293-303. CrossRef PubMed
  4.  
  5. Bostrom K., Tsao D., Shen S., Wang Y., Demer L.L. Matrix GLA protein modulates differentiation induced by bone morphogenetic protein-2 in C3H10T1. 2 cells . J. Biol. Chem. 2001. 276. P. 14044-14052. CrossRef PubMed
  6.  
  7. Bostrom K., Watson K.E., Horn S., Wortham C, Herman I.M., Demer L.L. Bone morphogenetic expres­sion in human atherosclerotic lesions . J. Clin. Invest. 1993. 91. P. 1800-1809. CrossRef PubMed PubMedCentral
  8.  
  9. Briehl M.M., Miesfeld R.L. Isolation and characte­rization of transcripts induced by androgen withdrawal and apoptotic cell death in the rat ventral prostate . Mol. Endocrinol. 1991. 5. P. 1318-1388. CrossRef PubMed
  10.  
  11. Cancela L., Hsiehg C. L., Francket U., Price P.A. Mo­lecular structure, chromosome assignment, and pro­moter organization of the human matrix Gla protein gene . J. Biol. Chem. 1990. 265. P. 15040-15048.
  12.  
  13. Cancela M.L., Hu B., Price P.A. Effect of cell density and growth factors on matrix Gla protein expression by normal rat kidney cells . J. Cell. Physiol. 1997. 171. P. 125-134. CrossRef  
  14. Cancela M.L., Price P.A. Retinoic acid induces matrix Gla protein gene expression in human bone cells . En­docrinology. 1992. 130. P. 102-108. CrossRef PubMed
  15.  
  16. Coppinger J.A., Cagney G., Toomey S. Characteri­zation of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions . Blood. 2004. 103. P. 2096-2104. CrossRef PubMed
  17.  
  18. Farzaneh-Far A., Davies J.D., Braam L.A., Spronk H.M., Proudfoot D., Chan S.W., O'Shaughnessy K.M., Weissberg P.L., Vermeer C, Shanaham CM. A Poly­morphism of the human matrix g-carboxyglutamic acid protein promoter alters binding of an activating pro-tein-1 complex and is associated with altered transcrip­tion and serum levels . J. Biol. Chem. 2001. 276. P. 32466-32473. CrossRef PubMed
  19.  
  20. Farzaneh-Far A., Proudfoot D., Weissberg P.L., Shanahan CM. Matrix gla protein is regulated by a mechanism functionally related to the calcium-sensing receptor . Biochem. and Biophys. Res. Commun. 2000. 277. P. 736-740. CrossRef PubMed
  21.  
  22. Farzaneh-Far A., Weissberg P.L., Proudfoot D., Shanahan CM. Transcriptional regulation of matrix gla protein . Z. Kardiol.- 2001. 90, Suppl. 3. P. 38-42. 13.Fraser J.D., Otawara Y, Price P.A. 1,25-Dihydroxy-vitamin D3 stimulates the synthesis of matrix r-carboxyglutamic acid protein by osteosarcoma cells . J. Biol. Chem. 1988. 263. P. 911-916. CrossRef PubMed
  23.  
  24. Fraser J.D., Price P.A. Induction of matrix Gla protein synthesis during prolonged 1,25-dihydroxyvitamin D3 treatment of osteosarcoma cells . Calcif. Tissue Int. 1990. 46. P. 270-279. CrossRef PubMed
  25.  
  26. Fraser J.D., Price P.A. Lung, heart, and kidney express high levels of mRNA for the vitamin K-dependent matrix Gla protein . J. Biol. Chem. 1988. 263. P. 11033-11036.
  27.  
  28. Fukui N., Zhu Y, Maloney W.J., Clohisy J., Sandell L.J. Stimulation of BMP-2 expression by pro­inflammatory cytokines IL-1 and TNF-alpha in normal and osteoarthritic chondrocytes . J. Bone Joint Surg. Amer. 2003. 85 (A Suppl. 3). P. 59-66. CrossRef PubMed
  29.  
  30. Hackeng T.M., Rosing J., Spronk H.M., Vermeer C. Total chemical synthesis of human matrix Gla protein . Protein Sci. 2001. 10. P. 864-870. CrossRef PubMed PubMedCentral
  31.  
  32. Hale J.E., Fraser J.D., Price P.A. The identification of matrix Gla protein in cartilage . J. Biol. Chem. 1988. 263. P. 5820-5824.
  33.  
  34. Hale J.E., Williamson M.K., Price P.A. Carboxyl-terminal proteolytic processing of matrix Gla protein . Ibid. 1991. 266. P. 21145-21149.
  35.  
  36. Herrmann S.M., Whatling C, Brand E., Nikaud , Gariepy J., Simon A., Evans A., Ruidavets L.B., Arveiler D., Luc G., Tiret L., Henney A., Cambien F. Polymorphisms of the human matrix Gla protein (MGP) gene, vascular calcification, and myocardial infarction . Arterioscler. Thromb. Vasc. Biol. 2000. 20. P. 2386-2393. CrossRef PubMed
  37.  
  38. Holbrook A.M., Pereira J.A., Labiris R. McDonald H., Douketis J.D., Crowther M., Wells P.S. Systematic overview of warfarin and its drug and food interactions . Arch. Intern. Med. 2005. 165. P. 1095-1106. CrossRef PubMed
  39.  
  40. Hruska K.A., Mathew S., Saab G. Bone morphogenetic proteins in vascular calcification . Circulat. Res. 2005. 97. P. 105-114. CrossRef PubMed
  41.  
  42. Jeziorska M., McCollum C, Wooley D.E. Observa­tions on bone formation and remodelling in advanced atherosclerotic lesions of human carotid arteries . Virchows Arch. 1998. 433. P. 559-565. CrossRef PubMed
  43.  
  44. Kirfel J., Kelter M., Cancela L.M., Price P.A., Schule R. Identification of a novel negative retinoic acid responsive element in the promoter of the human matrix Gla protein gene . Proc. Natl. Acad. Sci. USA. 1997. 94. P. 2227-2232. CrossRef PubMed PubMedCentral
  45.  
  46. Kobayashi N., Kitazawa R., Maeda S., Schurgers L.J., Kitazawa S. T-138C polymorphism of matrix Gla pro­tein promoter alters its expression but is not directly associated with atherosclerotic vascular calcification .Kobe J. Med. Sci. 2004. 50. P. 69-81.
  47.  
  48. Levy R.J., Howard S.L., Oshry L.J. Carboxyglutamic acid (Gla) containing proteins of human calcified atherosclerotic plaque solubilized by EDTA . Atherosclerosis. 1986. 59. P.155-160. CrossRef  
  49. Levy R.J., Lian J.B., Gallop P. Atherocalcin, a r-carboxyglutamic acid containing protein from athero­sclerotic plaque . Biochem. and Biophys. Res. Commun. 1979. 91. P. 41-49. CrossRef  
  50. Lian J.B., Skinner M., Glimcher M.J., Gallop P. The presence of g-carboxyglutamic acid in the proteins associated with ectopic calcification . Ibid. 1976. 73. P. 349-356. CrossRef  
  51. Loeser R., Carlson C.S., Tulli H., Jerome W.G., Miller L., Wallin R. Articular-cartilage matrix gamma-carboxyglutamic acid-containing protein. Characte­rization and immunolocalization . Biochem. J. 1992. 282 (Pt 1). P. 1-6. CrossRef PubMed PubMedCentral
  52.  
  53. Luo G., Ducy P., McKee M.D., Pinero G.J., Loyer E., Behringer R.R., Karsenty G. Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein . Nature. 1997. 386. P. 78-81. CrossRef PubMed
  54.  
  55. Masterjohn C. Vitamin D toxicity redefined: vitamin K and the molecular mechanism . Med. Hypoth. 2007. 68. P. 1026-1034. CrossRef PubMed
  56.  
  57. Meredith J.E., Fazeli B., Schwartz M.A. The extracellular matrix as a cell survival factor . Mol. Biol. Cell. 1993. 4.- P. 953-961. CrossRef PubMed PubMedCentral
  58.  
  59. Mori K., Shioi A., Jono S., Nishizawa Y, Morii H. Expression of matrix Gla protein (MGP) in an in vitro model of vascular calcification . FEBS Lett. 1998. 433. P. 19-22. CrossRef  
  60. Munroe P.B., Olgunturk R.O., Fryns J.P., Van Maldergem L., Ziereisen F., Yuksel B., Gardiner R.M., Chung E. Mutations in the gene encoding the human matrix Gla protein cause Keutel syndrome . Nat. Genet. 1999. 21. P. 142-144. CrossRef PubMed
  61.  
  62. Murshed M., Schinke T., McKee M.D., Karsenty G. Extra cellular matrix mineralization is regulated locally: different roles of two gla-containing proteins . J. Cell. Biol. 2004. 165. P. 625-630. CrossRef PubMed PubMedCentral
  63.  
  64. Newman B., Gigout L.I., Sudre L., Grant M.E., Wallis G.A. Coordinated expression of matrix Gla protein is required during endochondral ossification for chondro­cyte survival . J. Cell Biol. 2001. 154. P. 659-666. CrossRef PubMed PubMedCentral
  65.  
  66. Nishimoto S.K., Nishimoto M. Matrix Gla protein C-terminal region binds to vitronectin. Co-localization suggests binding occurs during tissue development . Matrix Biol- 2005. 24. P. 353-361. CrossRef PubMed
  67.  
  68. Owen T.A., Aronow M.S., Barone L.M., Bettencourt B., Stein G.S., Lian J.B. Pleiotropic effects of vitamin D on osteoblast gene expression are related to the proliferative and differentiated state of the bone cell phenotype: Dependency upon basal levels of gene ex­pression, duration of exposure, and bone matrix competency in normal rat osteoblast cultures . Endocrinology. 1991. 128. P 1496-1504. CrossRef PubMed
  69.  
  70. Parhami F., Morrow A.D., Balucan J., Leitinger N., Watson A.D., Tintut Y., Berliner J.A., Demer L.L. Lipid oxidation products have opposite effects on calcifying vascular cell and bone cell differentiation. A possible explanation for the paradox of arterial calcification in osteoporotic patients . Arterioscler. Thromb. Vasc. Biol. 1997. 17. P. 680-687. CrossRef PubMed
  71.  
  72. Pereira L., Andrikopoulos K., Tian J., Lee S.Y, Keene D.R., Ono R., Reinhardt D.P., Sakai L.Y, Biery N.J., Bunton T., Dietz H.C., Ramirez F. Targeting of the gene encoding fibrillin-1 recapitulates the vascular aspect of Marfan syndrome . Nat. Genet. 1997. 17. P. 218-222. CrossRef PubMed
  73.  
  74. Pereira L., Lee S.Y, Gayraud B., Andrikopoulos K., Shapiro S.D., Bunton T., Biery N.J., Dietz H.C., Sakai L.Y, Ramirez F. Pathogenetic sequence for aneurysm revealed in mice underexpressing fibrillin-1 . Proc. Natl. Acad. Sci. USA. 1999. 96. P. 3819-3823. CrossRef PubMed PubMedCentral
  75.  
  76. Price P.A., Chan W.S., Jolson D.M., Williamson M.K. The elastic lamellae of devitalized arteries calcify when incubated in serum. Evidence for a serum calcification factor . Arterioscler. Thromb. Vasc. Biol. 2006. 26. P. 1079-1085. CrossRef PubMed
  77.  
  78. Price P.A., Faus S.A., Williamson M.K. Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves . Ibid. 1998. 18. P. 1400-1407. CrossRef PubMed
  79.  
  80. Price P.A., Faus S.A., Williamson M.K. Warfarin-iduced artery calcification is accelerated by growth and vitamin D . Ibid. 2000. 20. P. 317-327. CrossRef PubMed
  81.  
  82. Price P.A., Kaneda Y Vitamin K counteracts the effect of warfarin in liver but not in bone . Thrombosis. 1987. 46. P. 121-131. CrossRef  
  83. Price P.A., Rice J.S., Williamson M.K. Conserved phosphorylation of serines in the Ser-X-Glu. Ser(P) sequences of the vitamin K-dependent matrix Gla protein from shark, lamb, rat, cow, and human . Protein Sci. 1994. 3. P. 822-830. CrossRef PubMed PubMedCentral
  84.  
  85. Price P.A., Sloper S.A. Concurrent warfarin treatment further reduces bone mineral levels in 1,25-dihydro-xyvitamin D3-treated rats . J. Biol. Chem. 1983. 258. P. 6004-6007.
  86.  
  87. Price P.A., Thomas G.R., Pardini A.W., Figueira W.F., Caputo J.M., Williamson M.K. Discovery of a high molecular weight complex of calcium, phosphate, fetuin, and matrix gamma-carboxyglutamic acid protein in the serum of etidronate-treated rats . Ibid. 2002. 277. P. 3926-3934. CrossRef PubMed
  88.  
  89. Price P.A., Urist M.R., Otawara Y Matrix Gla protein, a new g-carboxyglutamic acid-containing protein which is associated with the organic matrix of bone . Biochem. and Biophys. Res. Commun. 1983. 117. P. 765-771. CrossRef  
  90. Price P.A., Williamson M.K. Effects of warfarin on bone: studies on the vitamin K-dependent protein of rat bone . J. Biol. Chem. 1981. 256. P. 12754-12759.
  91.  
  92. Price P.A., Williamson M.K. Primary structure of bo­vine matrix Gla protein, a new vitamin K-dependentbone protein . J. Biol. Chem. 1985. 260. P. 14971-14975.
  93.  
  94. Proudfoot D., Shanahan CM. Molecular mechanisms mediating vascular calcification: role of matrix Gla protein . Nephrology (Carlton). 2006. 11. P. 455-461. CrossRef PubMed
  95.  
  96. Proudfoot D., Skepper J.N., Hegyi L., Bennett M.R., Shanahan C.M., Peter L., Weissberg P.L. Apoptosis regulates human vascular calcification in vitro. Evidence for initiation of vascular calcification by apoptotic bodies . Circulat. Res. 2000. 87. P. 1055-1062. CrossRef PubMed
  97.  
  98. Proudfoot D., Skepper J.N., Hegyi L., Farzaneh-Far A., Shanahan C.M., Weissberg P.L. The role of apoptosis in the initiation of vascular calcification . Z. Kardiol. 2001. 90. P. 43-46. CrossRef PubMed
  99.  
  100. Proudfoot D., Skepper J.N., Shanahan C.M., Weissberg P.L. Calcification of human vascular cells in vitro is correlated with high levels of matrix Gla protein and low levels of osteoontin expression . Arterioscler. Thromb. Vasc. Biol. 1998. 18. P. 379-388. CrossRef PubMed
  101.   Rannels S.R., Cancela M.L., Wolpert E.B., Price P.A. Matrix Gla protein mRNA expression in cultured type II pneumocytes . Amer. J. Physiol. 1993. 265. P L270-L278 CrossRef PubMed  
  102. Reddi A.H., Reddi A. Bone morphogenetic proteins (BMPs): from morphogens to metabologens . Cyto­kine Growth Factor Re. 2009. 20. P. 341-342. CrossRef PubMed
  103.  
  104. Reynolds J.L., Joannides A.J., Skepper J.N., McNair R., Schurgers L.J., Proudfoot D., Jahnen-Dechent W., Weissberg P.L., 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. Amer. Soc. Nephrol. 2004. 15. P. 2857-2867. CrossRef PubMed
  105.  
  106. Rice J.S., Williamson M.K., Price P.A. Isolation and sequence of the vitamin K-dependent matrix Gla protein from the calcified cartilage of the soupfin shark . J. Bone Min. Res. 1994. 9. P. 567-576. CrossRef PubMed
  107.  
  108. Roy M.E., Nishimoto S.K. Matrix Gla protein binding to hydroxyapatite is dependent on the ionic environ­ment: Calcium enhances binding affinity but phosphate and magnesium decrease affinity . Bone. 2002. 31. P. 296-302. CrossRef  
  109. Sato Y., Nakamura R., Satoh M., Fujishita K., Mori S., Ishida S., Yamaguchi T., Inoue K., Nagao T., Ohno Y Thyroid hormone targets matrix Gla protein gene associated with vascular smooth muscle calcification . Circulat. Res. 2005. 97. P. 550-557. CrossRef PubMed
  110.  
  111. Schoppet M., Al-Fakhri N., Franke F.E., Katz N., Barth P.J., Maisch B., Preissner K.T., Hofbauer L.C Localization of osteoprotegerin, tumor necrosis fac­tor-related apoptosis-inducing ligand, and receptor activator of nuclear factor-kB ligand in Minckeberg's sclerosis and atherosclerosis . J. Clin. Endocrinol. and Metabol. 2004. 89. P. 4104-4112. CrossRef PubMed
  112.  
  113. Schurgers L.J., Teunissen K.J., Knapen M.H., Kwaijtaal M., van Diest R., Appels A., Reutelingsperger C.P., Cleutjens J.P., Vermeer C. Novel conformation-specific antibodies against matrix gamma-carboxyglutamic acid (Gla) protein: undercarboxylated matrix Gla protein as marker for vascular calcification . Arterioscler. Thromb. Vasc. Biol. 2005. 25. P. 1629-1633. CrossRef PubMed
  114.  
  115. Severson A.R., Ingram R.T., Fitzpatrick L.A. Matrix proteins associated with bone calcification are present in human vascular smooth muscle cells grown in vitro . In Vitro Cell. De Biol. 1995. 31. P. 853-857. CrossRef PubMed
  116.  
  117. Shanahan C.M., Cary N.R., Metcalfe J.C., Weissberg P.L. High expression of genes for calcification regulating proteins in human atherosclerotic plaques . J. Clin. Invest. 1994. 93. P. 2393-2402. CrossRef PubMed PubMedCentral
  118.  
  119. Shanahan C.M., Cary N.R., Salisbury J.R., Proudfoot D., Weissberg P.L., Edmonds M.E. Medial localization of mineralization-regulating proteins in association with Monckeberg's sclerosis: evidence for smooth muscle cell-mediated vascular calcification . Circulation. 1999. 100. P. 2168-2176. CrossRef PubMed
  120.  
  121. Shanahan C.M., Proudfoot D., Tyson K.L., Cary N. R. B., Edmonds M., Weissberg P. L. Expression of mineralisation-regulating proteins in association with human vascular calcification . Z. Kardiol. 2000. 89, Suppl. 2. P. II. 63-II. 68. CrossRef PubMed
  122.  
  123. Shanahan C.M., Weissberg P.L., Metcalfe J.C. Isola­tion of gene markers of differentiated and proliferating vascular smooth muscle cells . Circulat. Res. 1993. 73. P. 193-204. CrossRef PubMed
  124.  
  125. Singleton E.B., Merten D.F. An unusual syndrome of widened medullary cavities of the metacarpals and phalanges, aortic calcification and abnormal dentition . . Pediatr. Radiol. 1973. 1. P. 2-7. CrossRef PubMed
  126.  
  127. Spronk H.M., Soute B.A., Schurgers L.J., Cleutjens J.P., Thijssen H.H., De Mey J.G., Vermeer C. Matrix Gla protein accumulates at the border of regions of calcification and normal tissue in the media of the arterial vessel wall . Biochem. and Biophys. Res. Commun. 2001. 289. P. 485-490. CrossRef PubMed
  128.  
  129. Steitz S.A., Speer M.Y., McKee M.D., Liaw L., Almeida M., Yang H., Giachelli C.M. Osteopontin inhibits mineral deposition and promotes regression of ectopic calcification . Amer. J. Pathol. 2002. 161. P. 2035-2046. CrossRef  
  130. Stheneur C., Dumontier M.F., Guedes C. Fulchignoni-Lataud M.C., Tahiri K., Karsenty G., Corvol M.T. Basic fibroblast growth factor as a selective inducer of matrix Gla protein gene expression in proliferative chondrocytes . Biochem. J. 2003. 369. P. 63-70. CrossRef PubMed PubMedCentral
  131.  
  132. Sweatt A., Sane D.C., Hutson S.M., Wallin L.. Matrix Gla protein (MGP) and bone morphogenetic protein-2 in aortic calcified lesions of aging rats . J. Thromb. Haemost. 2003. 1. P. 178-185. CrossRef PubMed
  133.  
  134. Towler D.A., Bidder M., Latifi T., Coleman T., Semenkovich C.F. Diet-induced diabetes activates an osteogenic gene regulatory program in the aortas of low density lipoprotein receptor-deficient mice . J.Biol. Chem. 1998. 273. P. 30427-30434. CrossRef PubMed
  135.  
  136. Tyson K.L., Reynolds J.L., McNair R., Zhang Q., Weissberg P.L., Shanahan C.M. Osteo. chondrocytic tran­scription factors and their target genes exhibit distinct patterns of expression in human arterial calcification . Arterioscler. Thromb. Vasc. Biol. 2003. 23. P. 489-494. CrossRef PubMed
  137.  
  138. Urist M.R. Bone: formation by autoinduction . Sci­ence. 1965. 150. P. 893-899. CrossRef PubMed
  139.  
  140. Wajih N., Borras T., Xue W., Hutson S.M., Wallin R. Processing and transport of matrix gamma-carboxy-glutamic acid protein and bone morphogenetic protein-2 in cultured human vascular smooth muscle cells: Evidence for an uptake mechanism for serum fetuin . J. Biol. Chem. 2004. 279. P. 43052-43060. CrossRef PubMed
  141.  
  142. Wajih N., Sane D.C., Hutson S.M., Wallin R. The inhibitory effect of calumenin on the vitamin K-dependent gamma-carboxylation system. Characte­rization of the system in normal and warfarin-resistant rats . Ibid. P. 276-283.
  143.  
  144. Wallin R., Schurgers L., Wajih N. Effects of the blood coagulation vitamin K as an inhibitor of arterial calcification . Thromb. Res. 2008. 122. P. 411-417. CrossRef PubMed PubMedCentral
  145.  
  146. Yabe D., Nakamura T., Kanazawa N., Tashiro K., Honjo T. Calumenin, a Ca2+-binding protein retained in the endoplasmic reticulum with a novel carboxyl-terminal sequence, HDEF . J. Biol. Chem. 1997. 272. P. 232-239. CrossRef PubMed
  147.  
  148. Yagami K., Suh J.Y., Enomoto-Iwamoto M., Koyama E., Abrams W.R., Shapiro I.M., Pacifici M., Iwamoto M. Matrix Gla protein is a developmental regulator of chondrocyte mineralization and, when constitutively expressed, blocks endochondral and intramembranous ossification in the limb . J. Cell. Biol. 1999. 147. P. 1097-1108. CrossRef PubMed PubMedCentral
  149.  
  150. Yang H., Curinga G., Giachelli C.M. Elevated extracellular calcium levels induce smooth muscle cell matrix mineralization in vitro . Kidney Int. 2004. 66. P. 2293-2299. CrossRef PubMed
  151.  
  152. Zebboudj A.F., Imura M., Bostrom K. Matrix GLA protein, a regulatory protein for bone morphogenetic protein-2 . J. Biol. Chem. 2002. 277. P. 4388- 4394. CrossRef PubMed
  153.  
  154. Zhao J., Warburton D. Matrix Gla protein gene expression is induced by transforming growth factor-beta in embryonic lung culture . Amer. J. Physiol. 1997. 273, Pt.1. P. L282-L287. CrossRef PubMed
  155.  

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