Publication Type : Journal Article
Publisher : Cell Stem Cell,
Source : Cell Stem Cell, Volume 20, Number 2, p.218 - 232.e5 (2017)
Url : http://www.sciencedirect.com/science/article/pii/S1934590916303459
Campus : Amritapuri
School : School of Biotechnology
Department : biotechnology
Year : 2017
Abstract : Summary 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 innbsp;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.
Cite this Research Publication : Indulekha C. L. Pillai, Shen Li, Milagros Romay, Larry Lam, Yan Lu, Jie Huang, Nathaniel Dillard, Marketa Zemanova, Liudmilla Rubbi, Yibin Wang, Jason Lee, Ming Xia, Owen Liang, Ya-Hong Xie, Matteo Pellegrini, Aldons J. Lusis, and Arjun Deb, “Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification”, Cell Stem Cell, vol. 20, pp. 218 - 232.e5, 2017.