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AMPK deficiency in chondrocytes accelerated the progression of instability-induced and ageing-associated osteoarthritis in adult mice
Osteoarthritis (OA) is a progressive degenerative disease of the joints that is associated with both joint injury and ageing. Here, we investigated the role of the energy sensor AMP-activated protein kinase (AMPK) in maintaining a healthy state of articular cartilage and in OA development. Using car...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320548/ https://www.ncbi.nlm.nih.gov/pubmed/28225087 http://dx.doi.org/10.1038/srep43245 |
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author | Zhou, Sheng Lu, Wanli Chen, Liang Ge, Qiting Chen, Dongyang Xu, Zhihong Shi, Dongquan Dai, Jin Li, Jianxin Ju, Huangxian Cao, Yi Qin, Jinzhong Chen, Shuai Teng, Huajian Jiang, Qing |
author_facet | Zhou, Sheng Lu, Wanli Chen, Liang Ge, Qiting Chen, Dongyang Xu, Zhihong Shi, Dongquan Dai, Jin Li, Jianxin Ju, Huangxian Cao, Yi Qin, Jinzhong Chen, Shuai Teng, Huajian Jiang, Qing |
author_sort | Zhou, Sheng |
collection | PubMed |
description | Osteoarthritis (OA) is a progressive degenerative disease of the joints that is associated with both joint injury and ageing. Here, we investigated the role of the energy sensor AMP-activated protein kinase (AMPK) in maintaining a healthy state of articular cartilage and in OA development. Using cartilage-specific, tamoxifen-inducible AMPKα1 conditional knockout (AMPKα1 cKO), AMPKα2 conditional knockout (AMPKα2 cKO) and AMPKα1α2 conditional double knockout (AMPKα cDKO) mice, we found that compared with wild-type (WT) littermates, mutant mice displayed accelerated severity of surgically induced OA, especially AMPKα cDKO mice. Furthermore, male but not female AMPKα cDKO mice exhibited severely spontaneous ageing-associated OA lesions at 12 months of age. The chondrocytes isolated from AMPKα cDKO mice resulted in an enhanced interleukin-1β (IL-1β)-stimulated catabolic response. In addition, upregulated expression of matrix metalloproteinase-3 (MMP-3), MMP-13 and phospho-nuclear factor-κB (phospho-NF-κB) p65 and increased levels of apoptotic markers were detected in the cartilage of AMPKα cDKO mice compared with their WT littermates in vivo. Thus, our findings suggest that AMPK activity in chondrocytes is important in maintaining joint homeostasis and OA development. |
format | Online Article Text |
id | pubmed-5320548 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53205482017-03-01 AMPK deficiency in chondrocytes accelerated the progression of instability-induced and ageing-associated osteoarthritis in adult mice Zhou, Sheng Lu, Wanli Chen, Liang Ge, Qiting Chen, Dongyang Xu, Zhihong Shi, Dongquan Dai, Jin Li, Jianxin Ju, Huangxian Cao, Yi Qin, Jinzhong Chen, Shuai Teng, Huajian Jiang, Qing Sci Rep Article Osteoarthritis (OA) is a progressive degenerative disease of the joints that is associated with both joint injury and ageing. Here, we investigated the role of the energy sensor AMP-activated protein kinase (AMPK) in maintaining a healthy state of articular cartilage and in OA development. Using cartilage-specific, tamoxifen-inducible AMPKα1 conditional knockout (AMPKα1 cKO), AMPKα2 conditional knockout (AMPKα2 cKO) and AMPKα1α2 conditional double knockout (AMPKα cDKO) mice, we found that compared with wild-type (WT) littermates, mutant mice displayed accelerated severity of surgically induced OA, especially AMPKα cDKO mice. Furthermore, male but not female AMPKα cDKO mice exhibited severely spontaneous ageing-associated OA lesions at 12 months of age. The chondrocytes isolated from AMPKα cDKO mice resulted in an enhanced interleukin-1β (IL-1β)-stimulated catabolic response. In addition, upregulated expression of matrix metalloproteinase-3 (MMP-3), MMP-13 and phospho-nuclear factor-κB (phospho-NF-κB) p65 and increased levels of apoptotic markers were detected in the cartilage of AMPKα cDKO mice compared with their WT littermates in vivo. Thus, our findings suggest that AMPK activity in chondrocytes is important in maintaining joint homeostasis and OA development. Nature Publishing Group 2017-02-22 /pmc/articles/PMC5320548/ /pubmed/28225087 http://dx.doi.org/10.1038/srep43245 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Zhou, Sheng Lu, Wanli Chen, Liang Ge, Qiting Chen, Dongyang Xu, Zhihong Shi, Dongquan Dai, Jin Li, Jianxin Ju, Huangxian Cao, Yi Qin, Jinzhong Chen, Shuai Teng, Huajian Jiang, Qing AMPK deficiency in chondrocytes accelerated the progression of instability-induced and ageing-associated osteoarthritis in adult mice |
title | AMPK deficiency in chondrocytes accelerated the progression of instability-induced and ageing-associated osteoarthritis in adult mice |
title_full | AMPK deficiency in chondrocytes accelerated the progression of instability-induced and ageing-associated osteoarthritis in adult mice |
title_fullStr | AMPK deficiency in chondrocytes accelerated the progression of instability-induced and ageing-associated osteoarthritis in adult mice |
title_full_unstemmed | AMPK deficiency in chondrocytes accelerated the progression of instability-induced and ageing-associated osteoarthritis in adult mice |
title_short | AMPK deficiency in chondrocytes accelerated the progression of instability-induced and ageing-associated osteoarthritis in adult mice |
title_sort | ampk deficiency in chondrocytes accelerated the progression of instability-induced and ageing-associated osteoarthritis in adult mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5320548/ https://www.ncbi.nlm.nih.gov/pubmed/28225087 http://dx.doi.org/10.1038/srep43245 |
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