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Enhanced Circadian Clock in MSCs-Based Cytotherapy Ameliorates Age-Related Temporomandibular Joint Condyle Degeneration
Aging has been proven to be one of the major causes of temporomandibular joint (TMJ) disability and pain in older people. Peripheral circadian rhythms play a crucial role in endochondral ossification and chondrogenesis. However, the age-related alterations of circadian clock in TMJ structures are se...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508754/ https://www.ncbi.nlm.nih.gov/pubmed/34638972 http://dx.doi.org/10.3390/ijms221910632 |
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author | Cha, Sa Lee, Sueng-Min Wang, Jiangyue Zhao, Qing Bai, Ding |
author_facet | Cha, Sa Lee, Sueng-Min Wang, Jiangyue Zhao, Qing Bai, Ding |
author_sort | Cha, Sa |
collection | PubMed |
description | Aging has been proven to be one of the major causes of temporomandibular joint (TMJ) disability and pain in older people. Peripheral circadian rhythms play a crucial role in endochondral ossification and chondrogenesis. However, the age-related alterations of circadian clock in TMJ structures are seldom reported. In the current study, TMJ condyles were extracted from young (4-month-old), middle-aged (10-month-old), and old-aged (20-month-old) adults to detect the morphology and circadian oscillation changes in TMJ condyles with aging. The transcriptome profile of Bmal1-deleted bone-marrow mesenchymal stem cells (BMSCs) and controls were explored to reveal the circadian-related differences at the molecular level. Furthermore, the reparative effects of Bmal1-overexpressed BMSCs-based cytotherapy in aged TMJ condyles were investigated in vitro and in vivo. Aged TMJ condyles displayed damaged tissue structure and an abolished circadian rhythm, accompanied by a progressively decreasing chondrogenesis capability and bone turnover activities. The deletion of Bmal1 significantly down-regulated chondrogenesis-related genes Prg4, Sox9, and Col7a1. Bmal1-overexpressed BMSCs presented improved migration capability ex vivo and attenuated age-related TMJ condylar degeneration in vivo. These data demonstrate the crucial role of circadian timing in the maintenance of osteochondral homeostasis, and indicate the potential clinical prospects of circadian-modified MSCs therapy in tissue regeneration. |
format | Online Article Text |
id | pubmed-8508754 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85087542021-10-13 Enhanced Circadian Clock in MSCs-Based Cytotherapy Ameliorates Age-Related Temporomandibular Joint Condyle Degeneration Cha, Sa Lee, Sueng-Min Wang, Jiangyue Zhao, Qing Bai, Ding Int J Mol Sci Article Aging has been proven to be one of the major causes of temporomandibular joint (TMJ) disability and pain in older people. Peripheral circadian rhythms play a crucial role in endochondral ossification and chondrogenesis. However, the age-related alterations of circadian clock in TMJ structures are seldom reported. In the current study, TMJ condyles were extracted from young (4-month-old), middle-aged (10-month-old), and old-aged (20-month-old) adults to detect the morphology and circadian oscillation changes in TMJ condyles with aging. The transcriptome profile of Bmal1-deleted bone-marrow mesenchymal stem cells (BMSCs) and controls were explored to reveal the circadian-related differences at the molecular level. Furthermore, the reparative effects of Bmal1-overexpressed BMSCs-based cytotherapy in aged TMJ condyles were investigated in vitro and in vivo. Aged TMJ condyles displayed damaged tissue structure and an abolished circadian rhythm, accompanied by a progressively decreasing chondrogenesis capability and bone turnover activities. The deletion of Bmal1 significantly down-regulated chondrogenesis-related genes Prg4, Sox9, and Col7a1. Bmal1-overexpressed BMSCs presented improved migration capability ex vivo and attenuated age-related TMJ condylar degeneration in vivo. These data demonstrate the crucial role of circadian timing in the maintenance of osteochondral homeostasis, and indicate the potential clinical prospects of circadian-modified MSCs therapy in tissue regeneration. MDPI 2021-09-30 /pmc/articles/PMC8508754/ /pubmed/34638972 http://dx.doi.org/10.3390/ijms221910632 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Cha, Sa Lee, Sueng-Min Wang, Jiangyue Zhao, Qing Bai, Ding Enhanced Circadian Clock in MSCs-Based Cytotherapy Ameliorates Age-Related Temporomandibular Joint Condyle Degeneration |
title | Enhanced Circadian Clock in MSCs-Based Cytotherapy Ameliorates Age-Related Temporomandibular Joint Condyle Degeneration |
title_full | Enhanced Circadian Clock in MSCs-Based Cytotherapy Ameliorates Age-Related Temporomandibular Joint Condyle Degeneration |
title_fullStr | Enhanced Circadian Clock in MSCs-Based Cytotherapy Ameliorates Age-Related Temporomandibular Joint Condyle Degeneration |
title_full_unstemmed | Enhanced Circadian Clock in MSCs-Based Cytotherapy Ameliorates Age-Related Temporomandibular Joint Condyle Degeneration |
title_short | Enhanced Circadian Clock in MSCs-Based Cytotherapy Ameliorates Age-Related Temporomandibular Joint Condyle Degeneration |
title_sort | enhanced circadian clock in mscs-based cytotherapy ameliorates age-related temporomandibular joint condyle degeneration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508754/ https://www.ncbi.nlm.nih.gov/pubmed/34638972 http://dx.doi.org/10.3390/ijms221910632 |
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