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Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism
Bone remodeling consists of resorption by osteoclasts followed by formation by osteoblasts, and osteoclasts are a source of bone formation-stimulating factors. Here we utilize osteoclast ablation by denosumab (DMAb) and RNA-sequencing of bone biopsies from postmenopausal women to identify osteoclast...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946812/ https://www.ncbi.nlm.nih.gov/pubmed/31911667 http://dx.doi.org/10.1038/s41467-019-14003-6 |
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author | Weivoda, Megan M. Chew, Chee Kian Monroe, David G. Farr, Joshua N. Atkinson, Elizabeth J. Geske, Jennifer R. Eckhardt, Brittany Thicke, Brianne Ruan, Ming Tweed, Amanda J. McCready, Louise K. Rizza, Robert A. Matveyenko, Aleksey Kassem, Moustapha Andersen, Thomas Levin Vella, Adrian Drake, Matthew T. Clarke, Bart L. Oursler, Merry Jo Khosla, Sundeep |
author_facet | Weivoda, Megan M. Chew, Chee Kian Monroe, David G. Farr, Joshua N. Atkinson, Elizabeth J. Geske, Jennifer R. Eckhardt, Brittany Thicke, Brianne Ruan, Ming Tweed, Amanda J. McCready, Louise K. Rizza, Robert A. Matveyenko, Aleksey Kassem, Moustapha Andersen, Thomas Levin Vella, Adrian Drake, Matthew T. Clarke, Bart L. Oursler, Merry Jo Khosla, Sundeep |
author_sort | Weivoda, Megan M. |
collection | PubMed |
description | Bone remodeling consists of resorption by osteoclasts followed by formation by osteoblasts, and osteoclasts are a source of bone formation-stimulating factors. Here we utilize osteoclast ablation by denosumab (DMAb) and RNA-sequencing of bone biopsies from postmenopausal women to identify osteoclast-secreted factors suppressed by DMAb. Based on these analyses, LIF, CREG2, CST3, CCBE1, and DPP4 are likely osteoclast-derived coupling factors in humans. Given the role of Dipeptidyl Peptidase-4 (DPP4) in glucose homeostasis, we further demonstrate that DMAb-treated participants have a significant reduction in circulating DPP4 and increase in Glucagon-like peptide (GLP)-1 levels as compared to the placebo-treated group, and also that type 2 diabetic patients treated with DMAb show significant reductions in HbA1c as compared to patients treated either with bisphosphonates or calcium and vitamin D. Thus, our results identify several coupling factors in humans and uncover osteoclast-derived DPP4 as a potential link between bone remodeling and energy metabolism. |
format | Online Article Text |
id | pubmed-6946812 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69468122020-01-09 Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism Weivoda, Megan M. Chew, Chee Kian Monroe, David G. Farr, Joshua N. Atkinson, Elizabeth J. Geske, Jennifer R. Eckhardt, Brittany Thicke, Brianne Ruan, Ming Tweed, Amanda J. McCready, Louise K. Rizza, Robert A. Matveyenko, Aleksey Kassem, Moustapha Andersen, Thomas Levin Vella, Adrian Drake, Matthew T. Clarke, Bart L. Oursler, Merry Jo Khosla, Sundeep Nat Commun Article Bone remodeling consists of resorption by osteoclasts followed by formation by osteoblasts, and osteoclasts are a source of bone formation-stimulating factors. Here we utilize osteoclast ablation by denosumab (DMAb) and RNA-sequencing of bone biopsies from postmenopausal women to identify osteoclast-secreted factors suppressed by DMAb. Based on these analyses, LIF, CREG2, CST3, CCBE1, and DPP4 are likely osteoclast-derived coupling factors in humans. Given the role of Dipeptidyl Peptidase-4 (DPP4) in glucose homeostasis, we further demonstrate that DMAb-treated participants have a significant reduction in circulating DPP4 and increase in Glucagon-like peptide (GLP)-1 levels as compared to the placebo-treated group, and also that type 2 diabetic patients treated with DMAb show significant reductions in HbA1c as compared to patients treated either with bisphosphonates or calcium and vitamin D. Thus, our results identify several coupling factors in humans and uncover osteoclast-derived DPP4 as a potential link between bone remodeling and energy metabolism. Nature Publishing Group UK 2020-01-07 /pmc/articles/PMC6946812/ /pubmed/31911667 http://dx.doi.org/10.1038/s41467-019-14003-6 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Weivoda, Megan M. Chew, Chee Kian Monroe, David G. Farr, Joshua N. Atkinson, Elizabeth J. Geske, Jennifer R. Eckhardt, Brittany Thicke, Brianne Ruan, Ming Tweed, Amanda J. McCready, Louise K. Rizza, Robert A. Matveyenko, Aleksey Kassem, Moustapha Andersen, Thomas Levin Vella, Adrian Drake, Matthew T. Clarke, Bart L. Oursler, Merry Jo Khosla, Sundeep Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism |
title | Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism |
title_full | Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism |
title_fullStr | Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism |
title_full_unstemmed | Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism |
title_short | Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism |
title_sort | identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946812/ https://www.ncbi.nlm.nih.gov/pubmed/31911667 http://dx.doi.org/10.1038/s41467-019-14003-6 |
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