OBJECTIVE: Approximately 13% of aortic valves removed from patients with end-stage aortic valve disease contain heterotopic ossification (HO). Recently, we identified a novel population of circulating osteogenic precursor (COP) cells that are derived from bone marrow and have the capability to form bone. These cells are identified by coexpression of the osteogenic marker type 1 collagen or osteoclacin and the hematopoietic marker CD45. We tested the hypothesis that these cells may contribute to heart valve stenosis. METHODS AND RESULTS: Quantification of CD45(+) osteoclacin(+) COP cells by flow cytometry showed that they represent up to 1.1% of mononuclear cells. Clonally derived COP cells produce bone morphogenetic proteins 2 and 4 by immunohistochemical analysis. We reviewed 105 cases of end-stage aortic valvular disease and confirmed HO in 13 archived specimens. Using immunohistochemistry, we identified COP cells by coexpression of CD45 and type 1 collagen. There was a statistically significant association between the presence of COP cells and early HO lesions. COP cells were negligible in regions of unaffected valve leaflets (no HO) from the same individuals. CONCLUSIONS: This study provides the first evidence that osteogenic cells in the blood home to sites of vascular injury and are associated with HO formation in heart valves.
OBJECTIVE: Approximately 13% of aortic valves removed from patients with end-stage aortic valve disease contain heterotopic ossification (HO). Recently, we identified a novel population of circulating osteogenic precursor (COP) cells that are derived from bone marrow and have the capability to form bone. These cells are identified by coexpression of the osteogenic marker type 1 collagen or osteoclacin and the hematopoietic marker CD45. We tested the hypothesis that these cells may contribute to heart valve stenosis. METHODS AND RESULTS: Quantification of CD45(+) osteoclacin(+) COP cells by flow cytometry showed that they represent up to 1.1% of mononuclear cells. Clonally derived COP cells produce bone morphogenetic proteins 2 and 4 by immunohistochemical analysis. We reviewed 105 cases of end-stage aortic valvular disease and confirmed HO in 13 archived specimens. Using immunohistochemistry, we identified COP cells by coexpression of CD45 and type 1 collagen. There was a statistically significant association between the presence of COP cells and early HO lesions. COP cells were negligible in regions of unaffected valve leaflets (no HO) from the same individuals. CONCLUSIONS: This study provides the first evidence that osteogenic cells in the blood home to sites of vascular injury and are associated with HO formation in heart valves.
Authors: Sumitra Miriyala; Maria C Gongora Nieto; Christopher Mingone; Debra Smith; Sergey Dikalov; David G Harrison; Hanjoong Jo Journal: Circulation Date: 2006-06-12 Impact factor: 29.690
Authors: H J Medbury; S L S Tarran; A K Guiffre; M M Y Williams; T H Lam; M Vicaretti; J P Fletcher Journal: Int Angiol Date: 2008-04 Impact factor: 2.789
Authors: Lixin Kan; Yijie Liu; Tammy L McGuire; Diana M Palila Berger; Rajeshwar B Awatramani; Susan M Dymecki; John A Kessler Journal: Stem Cells Date: 2009-01 Impact factor: 6.277
Authors: Elena Aikawa; Matthias Nahrendorf; Jose-Luiz Figueiredo; Filip K Swirski; Timur Shtatland; Rainer H Kohler; Farouc A Jaffer; Masanori Aikawa; Ralph Weissleder Journal: Circulation Date: 2007-11-26 Impact factor: 29.690
Authors: Rose Du; Kan V Lu; Claudia Petritsch; Patty Liu; Ruth Ganss; Emmanuelle Passegué; Hanqiu Song; Scott Vandenberg; Randall S Johnson; Zena Werb; Gabriele Bergers Journal: Cancer Cell Date: 2008-03 Impact factor: 31.743
Authors: Vitali Y Lounev; Rageshree Ramachandran; Michael N Wosczyna; Masakazu Yamamoto; Andrew D A Maidment; Eileen M Shore; David L Glaser; David J Goldhamer; Frederick S Kaplan Journal: J Bone Joint Surg Am Date: 2009-03-01 Impact factor: 5.284
Authors: Paul B Yu; Donna Y Deng; Carol S Lai; Charles C Hong; Gregory D Cuny; Mary L Bouxsein; Deborah W Hong; Patrick M McManus; Takenobu Katagiri; Chetana Sachidanandan; Nobuhiro Kamiya; Tomokazu Fukuda; Yuji Mishina; Randall T Peterson; Kenneth D Bloch Journal: Nat Med Date: 2008-11-30 Impact factor: 53.440
Authors: J S Manavalan; S Cremers; D W Dempster; H Zhou; E Dworakowski; A Kode; S Kousteni; M R Rubin Journal: J Clin Endocrinol Metab Date: 2012-06-27 Impact factor: 5.958
Authors: Michael R Convente; Haitao Wang; Robert J Pignolo; Frederick S Kaplan; Eileen M Shore Journal: Curr Osteoporos Rep Date: 2015-04 Impact factor: 5.096
Authors: SongTing Shi; David J J de Gorter; Willem M H Hoogaars; Peter A C 't Hoen; Peter ten Dijke Journal: Cell Mol Life Sci Date: 2012-07-04 Impact factor: 9.261