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The histone demethylase KDM5C controls female bone mass by promoting energy metabolism in osteoclasts

Women experience osteoporosis at higher rates than men. Aside from hormones, the mechanisms driving sex-dependent bone mass regulation are not well understood. Here, we demonstrate that the X-linked H3K4me2/3 demethylase KDM5C regulates sex-specific bone mass. Loss of KDM5C in hematopoietic stem cel...

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Autores principales: Liu, Huadie, Zhai, Lukai, Liu, Ye, Lu, Di, Vander Ark, Alexandra, Yang, Tao, Krawczyk, Connie M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10075994/
https://www.ncbi.nlm.nih.gov/pubmed/37018401
http://dx.doi.org/10.1126/sciadv.adg0731
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author Liu, Huadie
Zhai, Lukai
Liu, Ye
Lu, Di
Vander Ark, Alexandra
Yang, Tao
Krawczyk, Connie M.
author_facet Liu, Huadie
Zhai, Lukai
Liu, Ye
Lu, Di
Vander Ark, Alexandra
Yang, Tao
Krawczyk, Connie M.
author_sort Liu, Huadie
collection PubMed
description Women experience osteoporosis at higher rates than men. Aside from hormones, the mechanisms driving sex-dependent bone mass regulation are not well understood. Here, we demonstrate that the X-linked H3K4me2/3 demethylase KDM5C regulates sex-specific bone mass. Loss of KDM5C in hematopoietic stem cells or bone marrow monocytes increases bone mass in female but not male mice. Mechanistically, loss of KDM5C impairs the bioenergetic metabolism, resulting in impaired osteoclastogenesis. Treatment with the KDM5 inhibitor reduces osteoclastogenesis and energy metabolism of both female mice and human monocytes. Our report details a sex-dependent mechanism for bone homeostasis, connecting epigenetic regulation to osteoclast metabolism and positions KDM5C as a potential target for future treatment of osteoporosis in women.
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spelling pubmed-100759942023-04-06 The histone demethylase KDM5C controls female bone mass by promoting energy metabolism in osteoclasts Liu, Huadie Zhai, Lukai Liu, Ye Lu, Di Vander Ark, Alexandra Yang, Tao Krawczyk, Connie M. Sci Adv Biomedicine and Life Sciences Women experience osteoporosis at higher rates than men. Aside from hormones, the mechanisms driving sex-dependent bone mass regulation are not well understood. Here, we demonstrate that the X-linked H3K4me2/3 demethylase KDM5C regulates sex-specific bone mass. Loss of KDM5C in hematopoietic stem cells or bone marrow monocytes increases bone mass in female but not male mice. Mechanistically, loss of KDM5C impairs the bioenergetic metabolism, resulting in impaired osteoclastogenesis. Treatment with the KDM5 inhibitor reduces osteoclastogenesis and energy metabolism of both female mice and human monocytes. Our report details a sex-dependent mechanism for bone homeostasis, connecting epigenetic regulation to osteoclast metabolism and positions KDM5C as a potential target for future treatment of osteoporosis in women. American Association for the Advancement of Science 2023-04-05 /pmc/articles/PMC10075994/ /pubmed/37018401 http://dx.doi.org/10.1126/sciadv.adg0731 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Biomedicine and Life Sciences
Liu, Huadie
Zhai, Lukai
Liu, Ye
Lu, Di
Vander Ark, Alexandra
Yang, Tao
Krawczyk, Connie M.
The histone demethylase KDM5C controls female bone mass by promoting energy metabolism in osteoclasts
title The histone demethylase KDM5C controls female bone mass by promoting energy metabolism in osteoclasts
title_full The histone demethylase KDM5C controls female bone mass by promoting energy metabolism in osteoclasts
title_fullStr The histone demethylase KDM5C controls female bone mass by promoting energy metabolism in osteoclasts
title_full_unstemmed The histone demethylase KDM5C controls female bone mass by promoting energy metabolism in osteoclasts
title_short The histone demethylase KDM5C controls female bone mass by promoting energy metabolism in osteoclasts
title_sort histone demethylase kdm5c controls female bone mass by promoting energy metabolism in osteoclasts
topic Biomedicine and Life Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10075994/
https://www.ncbi.nlm.nih.gov/pubmed/37018401
http://dx.doi.org/10.1126/sciadv.adg0731
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