title: The appearance and modulation of osteocyte marker expression during calcification of vascular smooth muscle cells.
abstract: BACKGROUND
  Vascular calcification is an indicator of elevated cardiovascular risk. Vascular smooth muscle cells (VSMCs), the predominant cell type involved in medial vascular calcification, can undergo phenotypic transition to both osteoblastic and chondrocytic cells within a calcifying environment.
  
  
  RESULTS
  In the present study, using in vitro VSMC calcification studies in conjunction with ex vivo analyses of a mouse model of medial calcification, we show that vascular calcification is also associated with the expression of osteocyte phenotype markers. As controls, the terminal differentiation of murine calvarial osteoblasts into osteocytes was induced in vitro in the presence of calcifying medium (containing ß-glycerophosphate and ascorbic acid), as determined by increased expression of the osteocyte markers DMP-1, E11 and sclerostin. Culture of murine aortic VSMCs under identical conditions confirmed that the calcification of these cells can also be induced in similar calcifying medium. Calcified VSMCs had increased alkaline phosphatase activity and PiT-1 expression, which are recognized markers of vascular calcification. Expression of DMP-1, E11 and sclerostin was up-regulated during VSMC calcification in vitro. Increased protein expression of E11, an early osteocyte marker, and sclerostin, expressed by more mature osteocytes was also observed in the calcified media of Enpp1(-/-) mouse aortic tissue.
  
  
  CONCLUSIONS
  This study has demonstrated the up-regulation of key osteocytic molecules during the vascular calcification process. A fuller understanding of the functional role of osteocyte formation and specifically sclerostin and E11 expression in the vascular calcification process may identify novel potential therapeutic strategies for clinical intervention.
authors: The Roslin Institute, The University of Edinburgh, Roslin, Midlothian, Scotland, United Kingdom.
authors: Dongxing
authors: D
authors: Zhu
authors: Neil Charles Wallace
authors: NC
authors: Mackenzie
authors: José Luis
authors: JL
authors: Millán
authors: Colin
authors: C
authors: Farquharson
authors: Vicky Elizabeth
authors: VE
authors: MacRae
references: J Bone Miner Res. 2008 Jun;23(6):860-9
references: 18269310
references: Am J Pathol. 2001 Feb;158(2):543-54
references: 11159191
references: Circulation. 2008 Apr 1;117(13):1693-700
references: 18362235
references: Semin Dial. 2007 Mar-Apr;20(2):103-9
references: 17374082
references: DNA Cell Biol. 2004 Mar;23(3):155-65
references: 15068585
references: Cardiovasc Res. 2005 May 1;66(2):324-33
references: 15820201
references: J Histochem Cytochem. 2008 Jun;56(6):561-7
references: 18319272
references: Nat Genet. 2003 Aug;34(4):379-81
references: 12881724
references: Ann N Y Acad Sci. 2007 Nov;1116:281-90
references: 17646259
references: J Bone Miner Res. 2003 May;18(5):807-17
references: 12733719
references: Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9445-9
references: 12082181
references: Circ Res. 2001 Dec 7;89(12):1147-54
references: 11739279
references: Bone. 1996 Apr;18(4):305-13
references: 8726386
references: Mol Cell Biol. 2007 Jun;27(12):4465-74
references: 17438129
references: J Endocrinol Invest. 2005;28(8 Suppl):15-7
references: 16323824
references: Nat Genet. 1998 Jul;19(3):271-3
references: 9662402
references: Circ Res. 2008 Mar 14;102(5):529-37
references: 18202319
references: J Bone Miner Res. 2001 Nov;16(11):2017-26
references: 11697797
references: Bone. 2010 Apr;46(4):1146-55
references: 20053388
references: Nat Genet. 2006 Nov;38(11):1310-5
references: 17033621
references: Bone. 2001 Aug;29(2):149-54
references: 11502476
references: Arterioscler Thromb Vasc Biol. 2004 Jul;24(7):1161-70
references: 15155384
references: Bone. 2008 Apr;42(4):606-15
references: 18280232
references: Mol Cell Biol. 2006 Jun;26(12):4539-52
references: 16738320
references: J Bone Miner Res. 2007 Nov;22(11):1700-10
references: 17638573
references: Circulation. 1999 Nov 23;100(21):2168-76
references: 10571976
references: Kidney Int. 2004 Dec;66(6):2293-9
references: 15569318
references: Bone. 1988;9(3):165-75
references: 2844214
references: J Endocrinol. 2006 May;189(2):319-28
references: 16648299
references: Kidney Int. 2008 May;73(9):1024-30
references: 18288101
references: Int J Biochem Cell Biol. 2009 Jun;41(6):1421-9
references: 19146981
references: Mol Cell Proteomics. 2010 Sep;9(9):2048-62
references: 20551380
references: J Clin Invest. 2005 May;115(5):1210-20
references: 15841209
references: Circulation. 2008 Jun 3;117(22):2938-48
references: 18519861
references: Bone. 1999 Oct;25(4):405-12
references: 10511106
references: Adv Dent Res. 1999 Jun;13:93-8
references: 11276754
references: J Cell Physiol. 2009 Feb;218(2):276-84
references: 18803233
references: Bone. 1996 Feb;18(2):125-32
references: 8833206
references: Bone. 2005 Jun;36(6):943-7
references: 15869924
references: Biochem Biophys Res Commun. 2010 Jan 29;392(1):36-40
references: 20043874
references: Arterioscler Thromb Vasc Biol. 2005 Apr;25(4):686-91
references: 15625282
references: Circ Res. 2006 Apr 14;98(7):905-12
references: 16527991
references: Cells Tissues Organs. 2009;189(1-4):6-11
references: 18728354
references: Bone. 1995 Sep;17(3):279-86
references: 8541142