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ADAMTS5 in Osteoarthritis: Biological Functions, Regulatory Network, and Potential Targeting Therapies

ADAMTS5 is involved in the pathogenesis of OA. As the major aggrecanase-degrading articular cartilage matrix, ADAMTS5, has been regarded as a potential target for OA treatment. We here provide an updated insight on the regulation of ADAMTS5 and newly discovered therapeutic strategies for OA. Pathoph...

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Autores principales: Jiang, Lejian, Lin, Jiachen, Zhao, Sen, Wu, Jiaqian, Jin, Yongming, Yu, Li, Wu, Nan, Wu, Zhihong, Wang, Yue, Lin, Mao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381022/
https://www.ncbi.nlm.nih.gov/pubmed/34434966
http://dx.doi.org/10.3389/fmolb.2021.703110
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author Jiang, Lejian
Lin, Jiachen
Zhao, Sen
Wu, Jiaqian
Jin, Yongming
Yu, Li
Wu, Nan
Wu, Zhihong
Wang, Yue
Lin, Mao
author_facet Jiang, Lejian
Lin, Jiachen
Zhao, Sen
Wu, Jiaqian
Jin, Yongming
Yu, Li
Wu, Nan
Wu, Zhihong
Wang, Yue
Lin, Mao
author_sort Jiang, Lejian
collection PubMed
description ADAMTS5 is involved in the pathogenesis of OA. As the major aggrecanase-degrading articular cartilage matrix, ADAMTS5, has been regarded as a potential target for OA treatment. We here provide an updated insight on the regulation of ADAMTS5 and newly discovered therapeutic strategies for OA. Pathophysiological and molecular mechanisms underlying articular inflammation and mechanotransduction, as well as chondrocyte hypertrophy were discussed, and the role of ADAMTS5 in each biological process was reviewed, respectively. Senescence, inheritance, inflammation, and mechanical stress are involved in the overactivation of ADAMTS5, contributing to the pathogenesis of OA. Multiple molecular signaling pathways were observed to modulate ADAMTS5 expression, namely, Runx2, Fgf2, Notch, Wnt, NF-κB, YAP/TAZ, and the other inflammatory signaling pathways. Based on the fundamental understanding of ADAMTS5 in OA pathogenesis, monoclonal antibodies and small molecule inhibitors against ADAMTS5 were developed and proved to be beneficial pre-clinically both in vitro and in vivo. Recent novel RNA therapies demonstrated potentials in OA animal models. To sum up, ADAMTS5 inhibition and its signaling pathway–based modulations showed great potential in future therapeutic strategies for OA.
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spelling pubmed-83810222021-08-24 ADAMTS5 in Osteoarthritis: Biological Functions, Regulatory Network, and Potential Targeting Therapies Jiang, Lejian Lin, Jiachen Zhao, Sen Wu, Jiaqian Jin, Yongming Yu, Li Wu, Nan Wu, Zhihong Wang, Yue Lin, Mao Front Mol Biosci Molecular Biosciences ADAMTS5 is involved in the pathogenesis of OA. As the major aggrecanase-degrading articular cartilage matrix, ADAMTS5, has been regarded as a potential target for OA treatment. We here provide an updated insight on the regulation of ADAMTS5 and newly discovered therapeutic strategies for OA. Pathophysiological and molecular mechanisms underlying articular inflammation and mechanotransduction, as well as chondrocyte hypertrophy were discussed, and the role of ADAMTS5 in each biological process was reviewed, respectively. Senescence, inheritance, inflammation, and mechanical stress are involved in the overactivation of ADAMTS5, contributing to the pathogenesis of OA. Multiple molecular signaling pathways were observed to modulate ADAMTS5 expression, namely, Runx2, Fgf2, Notch, Wnt, NF-κB, YAP/TAZ, and the other inflammatory signaling pathways. Based on the fundamental understanding of ADAMTS5 in OA pathogenesis, monoclonal antibodies and small molecule inhibitors against ADAMTS5 were developed and proved to be beneficial pre-clinically both in vitro and in vivo. Recent novel RNA therapies demonstrated potentials in OA animal models. To sum up, ADAMTS5 inhibition and its signaling pathway–based modulations showed great potential in future therapeutic strategies for OA. Frontiers Media S.A. 2021-08-09 /pmc/articles/PMC8381022/ /pubmed/34434966 http://dx.doi.org/10.3389/fmolb.2021.703110 Text en Copyright © 2021 Jiang, Lin, Zhao, Wu, Jin, Yu, Wu, Wu, Wang and Lin. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Jiang, Lejian
Lin, Jiachen
Zhao, Sen
Wu, Jiaqian
Jin, Yongming
Yu, Li
Wu, Nan
Wu, Zhihong
Wang, Yue
Lin, Mao
ADAMTS5 in Osteoarthritis: Biological Functions, Regulatory Network, and Potential Targeting Therapies
title ADAMTS5 in Osteoarthritis: Biological Functions, Regulatory Network, and Potential Targeting Therapies
title_full ADAMTS5 in Osteoarthritis: Biological Functions, Regulatory Network, and Potential Targeting Therapies
title_fullStr ADAMTS5 in Osteoarthritis: Biological Functions, Regulatory Network, and Potential Targeting Therapies
title_full_unstemmed ADAMTS5 in Osteoarthritis: Biological Functions, Regulatory Network, and Potential Targeting Therapies
title_short ADAMTS5 in Osteoarthritis: Biological Functions, Regulatory Network, and Potential Targeting Therapies
title_sort adamts5 in osteoarthritis: biological functions, regulatory network, and potential targeting therapies
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381022/
https://www.ncbi.nlm.nih.gov/pubmed/34434966
http://dx.doi.org/10.3389/fmolb.2021.703110
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