Shared gene expression profiles in developing heart valves and osteoblast progenitor cells
1 Division of Molecular Cardiovascular Biology, Cincinnati Children's Medical Center, Cincinnati, Ohio 2 Division of Biomedical Informatics, Cincinnati Children's Medical Center, Cincinnati, Ohio The atrioventricular (AV) valves of the heart develop from undifferentiated mesenchymal endoca...
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Published in | Physiological genomics Vol. 35; no. 1; pp. 75 - 85 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Am Physiological Soc
17.09.2008
American Physiological Society |
Subjects | |
Online Access | Get full text |
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Summary: | 1 Division of Molecular Cardiovascular Biology, Cincinnati Children's Medical Center, Cincinnati, Ohio
2 Division of Biomedical Informatics, Cincinnati Children's Medical Center, Cincinnati, Ohio
The atrioventricular (AV) valves of the heart develop from undifferentiated mesenchymal endocardial cushions, which later mature into stratified valves with diversified extracellular matrix (ECM). Because the mature valves express genes associated with osteogenesis and exhibit disease-associated calcification, we hypothesized the existence of shared regulatory pathways active in developing AV valves and in bone progenitor cells. To define gene regulatory programs of valvulogenesis relative to osteoblast progenitors, we undertook Affymetrix gene expression profiling analysis of murine embryonic day (E)12.5 AV endocardial cushions compared with E17.5 AV valves (mitral and tricuspid) and with preosteoblast MC3T3-E1 (subclone4) cells. Overall, MC3T3 cells were significantly more similar to E17.5 valves than to E12.5 cushions, supporting the hypothesis that valve maturation involves the expression of many genes also expressed in osteoblasts. Several transcription factors characteristic of mesenchymal and osteoblast precursor cells, including Twist1 , are predominant in E12.5 cushion. Valve maturation is characterized by differential regulation of matrix metalloproteinases and their inhibitors as well as complex collagen gene expression. Among the most highly enriched genes during valvulogenesis were members of the small leucine-rich proteoglycan (SLRP) family including Asporin , a known negative regulator of osteoblast differentiation and mineralization. Together, these data support shared gene expression profiles of the developing valves and osteoblast bone precursor cells in normal valve development and homeostasis with potential functions in calcific valve disease.
microarray; heart valve maturation; asporin ; osteoglycin ; Twist1 ; collagen |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Address for reprint requests and other correspondence: K. E. Yutzey, Div. of Molecular Cardiovascular Biology, Cincinnati Children's Medical Center ML 7020, 240 Albert Sabin Way, Cincinnati, OH 45229 (e-mail: katherine.yutzey@cchmc.org). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. |
ISSN: | 1094-8341 1531-2267 |
DOI: | 10.1152/physiolgenomics.90212.2008 |