International Journal of Cardiology
Volume 139, Issue 2 , Pages 142-149 , 4 March 2010

Bone regulatory factors NFATc1 and Osterix in human calcific aortic valves

  • Alexandros Alexopoulos

      Affiliations

    • Department of Anatomy, School of Medicine, University of Patras, Greece
    • ,
  • Vasiliki Bravou

      Affiliations

    • Department of Anatomy, School of Medicine, University of Patras, Greece
    • ,
  • Stavros Peroukides

      Affiliations

    • Department of Anatomy, School of Medicine, University of Patras, Greece
    • ,
  • Loukas Kaklamanis

      Affiliations

    • Department of Pathology, Onassis Cardiac Surgery Center, Athens, Greece
    • ,
  • John Varakis

      Affiliations

    • Department of Anatomy, School of Medicine, University of Patras, Greece
    • ,
  • Dimitrios Alexopoulos

      Affiliations

    • Department of Cardiology, University Hospital of Patras, Greece
    • ,
  • Helen Papadaki

      Affiliations

    • Department of Anatomy, School of Medicine, University of Patras, Greece
    • Corresponding Author InformationCorresponding author. Department of Anatomy, School of Medicine, University of Patras, 26500 Rio, Patras, Greece. Tel.: +30 2610992391; fax: +30 2610997886.

Received 20 April 2008 ,Revised 26 August 2008 ,Accepted 12 October 2008.

References 

  1. Mohler ER, Gannon F, Reynolds C, Zimmerman R, Keane MG, Kaplan FS. Bone formation and inflammation in cardiac valves. Circulation. 2001;103:1522–1528
  2. Rajamannan NM, Subramaniam M, Rickard D, et al. Human aortic valve calcification is associated with an osteoblast phenotype. Circulation. 2003;107:2181–2184
  3. Shetty R, Pepin A, Charest A, et al. Expression of bone-regulatory proteins in human valve allografts. Heart. 2006;92:1303–1308
  4. Steiner I, Kašparová P, Kohout A, Dominik J. Bone formation in cardiac valves: a histopathological study of 128 cases. Virchows Arch. 2007;450:653–657
  5. O'Brien KD, Kuusisto J, Reichenbach DD, et al. Osteopontin is expressed in human aortic valvular lesions. Circulation. 1995;92:2163–2168
  6. Srivatsa SS, Harrity PJ, Maercklein PB, et al. Increased cellular expression of matrix proteins that regulate mineralization is associated with calcification of native human and porcine xenograft bioprosthetic heart valves. J Clin Invest. 1997;99:996–1009
  7. Liu AC, Joag VR, Gotlieb AI. The emerging role of valve interstitial cell phenotypes in regulating heart valve pathobiology. Am J Pathol. 2007;171:1407
  8. Durbin AD, Gotlieb AI. Advances towards understanding heart valve response to injury. Cardiovasc Pathol. 2002;11:69–77
  9. Taylor PM, Allen SP, Yacoub MH. Phenotypic and functional characterization of interstitial cells from human heart valves, pericardium and skin. J Heart Valve Dis. 2000;9:150–158
  10. Walker GA, Masters KS, Shah DN, Anseth KS, Leinwand LA. Valvular myofibroblast activation by transforming growth factor-β implications for pathological extracellular matrix remodeling in heart valve disease. Circ Res. 2004;95:253–260
  11. Rabkin-Aikawa E, Farber M, Aikawa M, Schoen FJ. Dynamic and reversible changes of interstitial cell phenotype during remodeling of cardiac valves. J Heart Valve Dis. 2004;13:841–847
  12. Mohler ER, Chawla MK, Chang AW, et al. Identification and characterization of calcifying valve cells from human and canine aortic valves. J Heart Valve Dis. 1999;8:254–260
  13. Cowell SJ, Newby DE, Boon NA, Elder AT. Calcific aortic stenosis: same old story?. Age Ageing. 2004;33:538–544
  14. Tu Q, Valverde P, Chen J. Osterix enhances proliferation and osteogenic potential of bone marrow stromal cells. Biochem Biophys Res Commun. 2006;341:1257–1265
  15. Meury T, Verrier S, Alini M. Human endothelial cells inhibit BMSC differentiation into mature osteoblasts in vitro by interfering with Osterix expression. J Cell Biochem. 2006;98:992–1006
  16. Fujita T, Azuma Y, Fukuyama R, et al. Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with PI3K-Akt signaling. J Cell Biol. 2004;166:85–95
  17. Hinoi E, Fujimori S, Wang L, Hojo H, Uno K, Yoneda Y. Nrf2 negatively regulates osteoblast differentiation via interfering with runx2-dependent transcriptional activation. J Biol Chem. 2006;281:18015
  18. Nakashima K, Zhou X, Kunkel G, et al. The novel zinc finger-containing transcription factor Osterix is required for osteoblast differentiation and bone formation. Cell. 2002;108:17–29
  19. Qu G, von Schroeder HP. Role of Osterix in endothelin-1-induced downregulation of vascular endothelial growth factor in osteoblastic cells. Bone. 2006;38:21–29
  20. Kim YJ, Kim HN, Park EK, et al. The bone-related Zn finger transcription factor Osterix promotes proliferation of mesenchymal cells. Gene. 2006;366:145–151
  21. Koga T, Matsui Y, Asagiri M, et al. NFAT and Osterix cooperatively regulate bone formation. Nat Med. 2005;11:880–885
  22. Horsley V, Pavlath GK. NFAT ubiquitous regulator of cell differentiation and adaptation. J Cell Biol. 2002;156:771–774
  23. Kiani A, Habermann I, Haase M, et al. Expression and regulation of NFAT (nuclear factors of activated T cells) in human CD34+ cells: down-regulation upon myeloid differentiation. J Leukoc Biol. 2004;76:1057–1065
  24. Marafiot T, Pozzobon M, Hansmann ML, et al. The NFATc1 transcription factor is widely expressed in white cells and translocates from the cytoplasm to the nucleus in a subset of human lymphomas. Br J Haematol. 2005;128:333–342
  25. Liu Z, Zhang C, Dronadula N, Li Q, Rao GN. Blockade of nuclear factor of activated T cells activation signaling suppresses balloon injury-induced neointima formation in a rat carotid artery model. J Biol Chem. 2005;280:14700–14708
  26. Serfling E, Chuvpilo S, Liu J, Höfer T, Palmetshofer A. NFATc1 autoregulation: a crucial step for cell-fate determination. Trends Immunol. 2006;27:461–469
  27. Hogan PG, Chen L, Nardone J, Rao A. Transcriptional regulation by calcium, calcineurin, and NFAT. Genes Dev. 2003;17:2205–2232
  28. Caira FC, Stock SR, Gleason TG, et al. Human degenerative valve disease is associated with up-regulation of low-density lipoprotein receptor-related protein 5 receptor-mediated bone formation. J Am Coll Cardiol. 2006;47:1707–1712
  29. Akiyama H, Chaboissier MC, Martin JF, Schedl A, de Crombrugghe B. The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6. Genes Dev. 2002;16:2813–2818
  30. Akiyama H, Chaboissier MC, Behringer RR, et al. Essential role of Sox9 in the pathway that controls formation of cardiac valves and septa. Proc Natl Acad Sci USA. 2004;101:6502–6507
  31. Lincoln J, Kist R, Scherer G, Yutzey KE. Sox9 is required for precursor cell expansion and extracellular matrix organization during mouse heart valve development. Dev Biol. 2007;305:120–132
  32. Tai G, Christodoulou I, Bishop AE, Polak JM. Use of green fluorescent fusion protein to track activation of the transcription factor Osterix during early osteoblast differentiation. Biochem Biophys Res Commun. 2005;333:1116–1122
  33. Ueta C, Iwamoto M, Kanatani N, et al. Skeletal malformations caused by overexpression of Cbfa1 or its dominant negative form in chondrocytes. J Cell Biol. 2001;153:87–100
  34. Takeda S, Bonnamy JP, Owen MJ, Ducy P, Karsenty G. Continuous expression of Cbfa1 in nonhypertrophic chondrocytes uncovers its ability to induce hypertrophic chondrocyte differentiation and partially rescues Cbfa1-deficient mice. Genes Dev. 2001;15:467–481
  35. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell. 1997;89:747–754
  36. Lian JB, Javed A, Zaidi SK, et al. Regulatory controls for osteoblast growth and differentiation: role of Runx/Cbfa/AML factors. Crit Rev Eukaryot Gene Expr. 2004;14:1–41
  37. Mathieu P, Voisine P, Pépin A, Shetty R, Savard N, Dagenais F. Calcification of human valve interstitial cells is dependent on alkaline phosphatase activity. J Heart Valve Dis. 2005;14:353–357
  38. Kaden JJ, Kiliç R, Sarikoç A, et al. Tumor necrosis factor alpha promotes an osteoblast-like phenotype in human aortic valve myofibroblasts: a potential regulatory mechanism of valvular calcification. Int J Mol Med. 2005;16:869–872
  39. Jian B, Narula N, Li QY, Mohler ER, Levy RJ. Progression of aortic valve stenosis: TGF-beta1 is present in calcified aortic valve cusps and promotes aortic valve interstitial cell calcification via apoptosis. Ann Thorac Surg. 2003;75:457–466
  40. Aikawa E, Nahrendorf M, Sosnovik D, et al. Multimodality molecular imaging identifies proteolytic and osteogenic activities in early aortic valve disease. Circulation. 2007;115:377–386
  41. Otto CM, Kuusisto J, Reichenbach DD, Gown AM, O'Brien KD. Characterization of the early lesion of degenerative valvular aortic stenosis. Histological and immunohistochemical studies. Circulation. 1994;90:844–853
  42. Kaden JJ, Dempfle CE, Grobholz R, et al. Interleukin-1 beta promotes matrix metalloproteinase expression and cell proliferation in calcific aortic valve stenosis. Atherosclerosis. 2003;170:205–211
  43. Kaden JJ, Dempfle CE, Grobholz R, et al. Inflammatory regulation of extracellular matrix remodeling in calcific aortic valve stenosis. Cardiovasc Pathol. 2005;14:80–87
  44. Guillotin B, Bourget C, Remy-Zolgadri M, et al. Human primary endothelial cells stimulate human osteoprogenitor cell differentiation. Cell Physiol Biochem. 2004;14:325–332
  45. Shin V, Zebboudj AF, Bostrom K. Endothelial cells modulate osteogenesis in calcifying vascular cells. J Vasc Res. 2004;41:193–201
  46. Armulik A, Abramsson A, Betsholtz C. Endothelial/pericyte interactions. Circ Res. 2005;97:512–523
  47. Coats AJ. Ethical authorship and publishing. Int J Cardiol. 2009;131:149–150

☆ This work was supported by the Postgraduate Programme on Basic Medical Sciences, Medical School, University of Patras, Greece.

PII: S0167-5273(08)01068-1

doi: 10.1016/j.ijcard.2008.10.014

International Journal of Cardiology
Volume 139, Issue 2 , Pages 142-149 , 4 March 2010

Article Tools

* Image Usage & Resolution