Cargando…
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...
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1783741285549473792 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8381022 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT jianglejian adamts5inosteoarthritisbiologicalfunctionsregulatorynetworkandpotentialtargetingtherapies AT linjiachen adamts5inosteoarthritisbiologicalfunctionsregulatorynetworkandpotentialtargetingtherapies AT zhaosen adamts5inosteoarthritisbiologicalfunctionsregulatorynetworkandpotentialtargetingtherapies AT wujiaqian adamts5inosteoarthritisbiologicalfunctionsregulatorynetworkandpotentialtargetingtherapies AT jinyongming adamts5inosteoarthritisbiologicalfunctionsregulatorynetworkandpotentialtargetingtherapies AT yuli adamts5inosteoarthritisbiologicalfunctionsregulatorynetworkandpotentialtargetingtherapies AT wunan adamts5inosteoarthritisbiologicalfunctionsregulatorynetworkandpotentialtargetingtherapies AT wuzhihong adamts5inosteoarthritisbiologicalfunctionsregulatorynetworkandpotentialtargetingtherapies AT wangyue adamts5inosteoarthritisbiologicalfunctionsregulatorynetworkandpotentialtargetingtherapies AT linmao adamts5inosteoarthritisbiologicalfunctionsregulatorynetworkandpotentialtargetingtherapies |