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Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification.

Publication ,  Journal Article
Pillai, ICL; Li, S; Romay, M; Lam, L; Lu, Y; Huang, J; Dillard, N; Zemanova, M; Rubbi, L; Wang, Y; Lee, J; Xia, M; Liang, O; Xie, Y-H ...
Published in: Cell Stem Cell
February 2, 2017

Mammalian tissues calcify with age and injury. Analogous to bone formation, osteogenic cells are thought to be recruited to the affected tissue and induce mineralization. In the heart, calcification of cardiac muscle leads to conduction system disturbances and is one of the most common pathologies underlying heart blocks. However the cell identity and mechanisms contributing to pathological heart muscle calcification remain unknown. Using lineage tracing, murine models of heart calcification and in vivo transplantation assays, we show that cardiac fibroblasts (CFs) adopt an osteoblast cell-like fate and contribute directly to heart muscle calcification. Small-molecule inhibition of ENPP1, an enzyme that is induced upon injury and regulates bone mineralization, significantly attenuated cardiac calcification. Inhibitors of bone mineralization completely prevented ectopic cardiac calcification and improved post injury heart function. Taken together, these findings highlight the plasticity of fibroblasts in contributing to ectopic calcification and identify pharmacological targets for therapeutic development.

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Published In

Cell Stem Cell

DOI

EISSN

1875-9777

Publication Date

February 2, 2017

Volume

20

Issue

2

Start / End Page

218 / 232.e5

Location

United States

Related Subject Headings

  • Pyrophosphatases
  • Phosphoric Diester Hydrolases
  • Phosphates
  • Osteogenesis
  • Myocardium
  • Myocardial Infarction
  • Mice, Inbred C57BL
  • Male
  • Humans
  • Fibroblasts
 

Citation

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Pillai, I. C. L., Li, S., Romay, M., Lam, L., Lu, Y., Huang, J., … Deb, A. (2017). Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification. Cell Stem Cell, 20(2), 218-232.e5. https://doi.org/10.1016/j.stem.2016.10.005
Pillai, Indulekha C. L., Shen Li, Milagros Romay, Larry Lam, Yan Lu, Jie Huang, Nathaniel Dillard, et al. “Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification.Cell Stem Cell 20, no. 2 (February 2, 2017): 218-232.e5. https://doi.org/10.1016/j.stem.2016.10.005.
Pillai ICL, Li S, Romay M, Lam L, Lu Y, Huang J, et al. Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification. Cell Stem Cell. 2017 Feb 2;20(2):218-232.e5.
Pillai, Indulekha C. L., et al. “Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification.Cell Stem Cell, vol. 20, no. 2, Feb. 2017, pp. 218-232.e5. Pubmed, doi:10.1016/j.stem.2016.10.005.
Pillai ICL, Li S, Romay M, Lam L, Lu Y, Huang J, Dillard N, Zemanova M, Rubbi L, Wang Y, Lee J, Xia M, Liang O, Xie Y-H, Pellegrini M, Lusis AJ, Deb A. Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification. Cell Stem Cell. 2017 Feb 2;20(2):218-232.e5.
Journal cover image

Published In

Cell Stem Cell

DOI

EISSN

1875-9777

Publication Date

February 2, 2017

Volume

20

Issue

2

Start / End Page

218 / 232.e5

Location

United States

Related Subject Headings

  • Pyrophosphatases
  • Phosphoric Diester Hydrolases
  • Phosphates
  • Osteogenesis
  • Myocardium
  • Myocardial Infarction
  • Mice, Inbred C57BL
  • Male
  • Humans
  • Fibroblasts