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Actomyosin contractility confers mechanoprotection against TNFα-induced disruption of the intervertebral disc
Inflammation triggers degradation of intervertebral disc extracellular matrix (ECM), a hallmark of disc degeneration that contributes to back pain. Mechanosensitive nucleus pulposus cells are responsible for ECM production, yet the impact of a proinflammatory microenvironment on cell mechanobiology...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438088/ https://www.ncbi.nlm.nih.gov/pubmed/32875103 http://dx.doi.org/10.1126/sciadv.aba2368 |
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author | Hernandez, Paula A. Jacobsen, Timothy D. Chahine, Nadeen O. |
author_facet | Hernandez, Paula A. Jacobsen, Timothy D. Chahine, Nadeen O. |
author_sort | Hernandez, Paula A. |
collection | PubMed |
description | Inflammation triggers degradation of intervertebral disc extracellular matrix (ECM), a hallmark of disc degeneration that contributes to back pain. Mechanosensitive nucleus pulposus cells are responsible for ECM production, yet the impact of a proinflammatory microenvironment on cell mechanobiology is unknown. Using gain- and loss-of-function approaches, we show that tumor necrosis factor–α (TNFα)–induced inflammation alters cell morphology and biophysical properties (circularity, contractility, cell stiffness, and hydraulic permeability) in a mechanism dependent on actomyosin contractility in a three-dimensional (3D) culture. We found that RhoA activation rescued cells from TNFα-induced mechanobiological disruption. Using a novel explant-in-hydrogel culture system, we demonstrate that nuclear factor kappa-B nuclear translocation and transcription are mechanosensitive, and its downstream effects on ECM degradation are regulated by actomyosin contractility. Results define a scaling relationship between circularity, contractility, and hydraulic permeability that is conserved from healthy to inflammatory microenvironments and is indicative of cell mechanobiological control across scales in 3D. |
format | Online Article Text |
id | pubmed-7438088 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-74380882020-08-31 Actomyosin contractility confers mechanoprotection against TNFα-induced disruption of the intervertebral disc Hernandez, Paula A. Jacobsen, Timothy D. Chahine, Nadeen O. Sci Adv Research Articles Inflammation triggers degradation of intervertebral disc extracellular matrix (ECM), a hallmark of disc degeneration that contributes to back pain. Mechanosensitive nucleus pulposus cells are responsible for ECM production, yet the impact of a proinflammatory microenvironment on cell mechanobiology is unknown. Using gain- and loss-of-function approaches, we show that tumor necrosis factor–α (TNFα)–induced inflammation alters cell morphology and biophysical properties (circularity, contractility, cell stiffness, and hydraulic permeability) in a mechanism dependent on actomyosin contractility in a three-dimensional (3D) culture. We found that RhoA activation rescued cells from TNFα-induced mechanobiological disruption. Using a novel explant-in-hydrogel culture system, we demonstrate that nuclear factor kappa-B nuclear translocation and transcription are mechanosensitive, and its downstream effects on ECM degradation are regulated by actomyosin contractility. Results define a scaling relationship between circularity, contractility, and hydraulic permeability that is conserved from healthy to inflammatory microenvironments and is indicative of cell mechanobiological control across scales in 3D. American Association for the Advancement of Science 2020-08-19 /pmc/articles/PMC7438088/ /pubmed/32875103 http://dx.doi.org/10.1126/sciadv.aba2368 Text en Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/ https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Hernandez, Paula A. Jacobsen, Timothy D. Chahine, Nadeen O. Actomyosin contractility confers mechanoprotection against TNFα-induced disruption of the intervertebral disc |
title | Actomyosin contractility confers mechanoprotection against TNFα-induced disruption of the intervertebral disc |
title_full | Actomyosin contractility confers mechanoprotection against TNFα-induced disruption of the intervertebral disc |
title_fullStr | Actomyosin contractility confers mechanoprotection against TNFα-induced disruption of the intervertebral disc |
title_full_unstemmed | Actomyosin contractility confers mechanoprotection against TNFα-induced disruption of the intervertebral disc |
title_short | Actomyosin contractility confers mechanoprotection against TNFα-induced disruption of the intervertebral disc |
title_sort | actomyosin contractility confers mechanoprotection against tnfα-induced disruption of the intervertebral disc |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438088/ https://www.ncbi.nlm.nih.gov/pubmed/32875103 http://dx.doi.org/10.1126/sciadv.aba2368 |
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