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Loss of Grem1-lineage chondrogenic progenitor cells causes osteoarthritis
Osteoarthritis (OA) is characterised by an irreversible degeneration of articular cartilage. Here we show that the BMP-antagonist Gremlin 1 (Grem1) marks a bipotent chondrogenic and osteogenic progenitor cell population within the articular surface. Notably, these progenitors are depleted by injury-...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618187/ https://www.ncbi.nlm.nih.gov/pubmed/37907525 http://dx.doi.org/10.1038/s41467-023-42199-1 |
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author | Ng, Jia Q. Jafarov, Toghrul H. Little, Christopher B. Wang, Tongtong Ali, Abdullah M. Ma, Yan Radford, Georgette A. Vrbanac, Laura Ichinose, Mari Whittle, Samuel Hunter, David J. Lannagan, Tamsin R. M. Suzuki, Nobumi Goyne, Jarrad M. Kobayashi, Hiroki Wang, Timothy C. Haynes, David R. Menicanin, Danijela Gronthos, Stan Worthley, Daniel L. Woods, Susan L. Mukherjee, Siddhartha |
author_facet | Ng, Jia Q. Jafarov, Toghrul H. Little, Christopher B. Wang, Tongtong Ali, Abdullah M. Ma, Yan Radford, Georgette A. Vrbanac, Laura Ichinose, Mari Whittle, Samuel Hunter, David J. Lannagan, Tamsin R. M. Suzuki, Nobumi Goyne, Jarrad M. Kobayashi, Hiroki Wang, Timothy C. Haynes, David R. Menicanin, Danijela Gronthos, Stan Worthley, Daniel L. Woods, Susan L. Mukherjee, Siddhartha |
author_sort | Ng, Jia Q. |
collection | PubMed |
description | Osteoarthritis (OA) is characterised by an irreversible degeneration of articular cartilage. Here we show that the BMP-antagonist Gremlin 1 (Grem1) marks a bipotent chondrogenic and osteogenic progenitor cell population within the articular surface. Notably, these progenitors are depleted by injury-induced OA and increasing age. OA is also caused by ablation of Grem1 cells in mice. Transcriptomic and functional analysis in mice found that articular surface Grem1-lineage cells are dependent on Foxo1 and ablation of Foxo1 in Grem1-lineage cells caused OA. FGFR3 signalling was confirmed as a promising therapeutic pathway by administration of pathway activator, FGF18, resulting in Grem1-lineage chondrocyte progenitor cell proliferation, increased cartilage thickness and reduced OA. These findings suggest that OA, in part, is caused by mechanical, developmental or age-related attrition of Grem1 expressing articular cartilage progenitor cells. These cells, and the FGFR3 signalling pathway that sustains them, may be effective future targets for biological management of OA. |
format | Online Article Text |
id | pubmed-10618187 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-106181872023-11-02 Loss of Grem1-lineage chondrogenic progenitor cells causes osteoarthritis Ng, Jia Q. Jafarov, Toghrul H. Little, Christopher B. Wang, Tongtong Ali, Abdullah M. Ma, Yan Radford, Georgette A. Vrbanac, Laura Ichinose, Mari Whittle, Samuel Hunter, David J. Lannagan, Tamsin R. M. Suzuki, Nobumi Goyne, Jarrad M. Kobayashi, Hiroki Wang, Timothy C. Haynes, David R. Menicanin, Danijela Gronthos, Stan Worthley, Daniel L. Woods, Susan L. Mukherjee, Siddhartha Nat Commun Article Osteoarthritis (OA) is characterised by an irreversible degeneration of articular cartilage. Here we show that the BMP-antagonist Gremlin 1 (Grem1) marks a bipotent chondrogenic and osteogenic progenitor cell population within the articular surface. Notably, these progenitors are depleted by injury-induced OA and increasing age. OA is also caused by ablation of Grem1 cells in mice. Transcriptomic and functional analysis in mice found that articular surface Grem1-lineage cells are dependent on Foxo1 and ablation of Foxo1 in Grem1-lineage cells caused OA. FGFR3 signalling was confirmed as a promising therapeutic pathway by administration of pathway activator, FGF18, resulting in Grem1-lineage chondrocyte progenitor cell proliferation, increased cartilage thickness and reduced OA. These findings suggest that OA, in part, is caused by mechanical, developmental or age-related attrition of Grem1 expressing articular cartilage progenitor cells. These cells, and the FGFR3 signalling pathway that sustains them, may be effective future targets for biological management of OA. Nature Publishing Group UK 2023-10-31 /pmc/articles/PMC10618187/ /pubmed/37907525 http://dx.doi.org/10.1038/s41467-023-42199-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Ng, Jia Q. Jafarov, Toghrul H. Little, Christopher B. Wang, Tongtong Ali, Abdullah M. Ma, Yan Radford, Georgette A. Vrbanac, Laura Ichinose, Mari Whittle, Samuel Hunter, David J. Lannagan, Tamsin R. M. Suzuki, Nobumi Goyne, Jarrad M. Kobayashi, Hiroki Wang, Timothy C. Haynes, David R. Menicanin, Danijela Gronthos, Stan Worthley, Daniel L. Woods, Susan L. Mukherjee, Siddhartha Loss of Grem1-lineage chondrogenic progenitor cells causes osteoarthritis |
title | Loss of Grem1-lineage chondrogenic progenitor cells causes osteoarthritis |
title_full | Loss of Grem1-lineage chondrogenic progenitor cells causes osteoarthritis |
title_fullStr | Loss of Grem1-lineage chondrogenic progenitor cells causes osteoarthritis |
title_full_unstemmed | Loss of Grem1-lineage chondrogenic progenitor cells causes osteoarthritis |
title_short | Loss of Grem1-lineage chondrogenic progenitor cells causes osteoarthritis |
title_sort | loss of grem1-lineage chondrogenic progenitor cells causes osteoarthritis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618187/ https://www.ncbi.nlm.nih.gov/pubmed/37907525 http://dx.doi.org/10.1038/s41467-023-42199-1 |
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