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Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis
Articular cartilage and synovial tissue from patients with osteoarthritis (OA) show an overactivity of connexin43 (Cx43) and accumulation of senescent cells associated with disrupted tissue regeneration and disease progression. The aim of this study was to determine the effect of oleuropein on Cx43...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485729/ https://www.ncbi.nlm.nih.gov/pubmed/32745074 http://dx.doi.org/10.18632/aging.103801 |
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author | Varela-Eirín, Marta Carpintero-Fernández, Paula Sánchez-Temprano, Agustín Varela-Vázquez, Adrián Paíno, Carlos Luis Casado-Díaz, Antonio Continente, Alfonso Calañas Mato, Virginia Fonseca, Eduardo Kandouz, Mustapha Blanco, Alfonso Caeiro, José Ramón Mayán, María D. |
author_facet | Varela-Eirín, Marta Carpintero-Fernández, Paula Sánchez-Temprano, Agustín Varela-Vázquez, Adrián Paíno, Carlos Luis Casado-Díaz, Antonio Continente, Alfonso Calañas Mato, Virginia Fonseca, Eduardo Kandouz, Mustapha Blanco, Alfonso Caeiro, José Ramón Mayán, María D. |
author_sort | Varela-Eirín, Marta |
collection | PubMed |
description | Articular cartilage and synovial tissue from patients with osteoarthritis (OA) show an overactivity of connexin43 (Cx43) and accumulation of senescent cells associated with disrupted tissue regeneration and disease progression. The aim of this study was to determine the effect of oleuropein on Cx43 and cellular senescence for tissue engineering and regenerative medicine strategies for OA treatment. Oleuropein regulates Cx43 promoter activity and enhances the propensity of hMSCs to differentiate into chondrocytes and bone cells, reducing adipogenesis. This small molecule reduce Cx43 levels and decrease Twist-1 activity in osteoarthritic chondrocytes (OACs), leading to redifferentiation, restoring the synthesis of cartilage ECM components (Col2A1 and proteoglycans), and reducing the inflammatory and catabolic factors mediated by NF-kB (IL-1ß, IL-6, COX-2 and MMP-3), in addition to lowering cellular senescence in OACs, synovial and bone cells. Our in vitro results demonstrate the use of olive-derived polyphenols, such as oleuropein, as potentially effective therapeutic agents to improve chondrogenesis of hMSCs, to induce chondrocyte re-differentiation in OACs and clearing out senescent cells in joint tissues in order to prevent or stop the progression of the disease. |
format | Online Article Text |
id | pubmed-7485729 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-74857292020-09-14 Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis Varela-Eirín, Marta Carpintero-Fernández, Paula Sánchez-Temprano, Agustín Varela-Vázquez, Adrián Paíno, Carlos Luis Casado-Díaz, Antonio Continente, Alfonso Calañas Mato, Virginia Fonseca, Eduardo Kandouz, Mustapha Blanco, Alfonso Caeiro, José Ramón Mayán, María D. Aging (Albany NY) Priority Research Paper Articular cartilage and synovial tissue from patients with osteoarthritis (OA) show an overactivity of connexin43 (Cx43) and accumulation of senescent cells associated with disrupted tissue regeneration and disease progression. The aim of this study was to determine the effect of oleuropein on Cx43 and cellular senescence for tissue engineering and regenerative medicine strategies for OA treatment. Oleuropein regulates Cx43 promoter activity and enhances the propensity of hMSCs to differentiate into chondrocytes and bone cells, reducing adipogenesis. This small molecule reduce Cx43 levels and decrease Twist-1 activity in osteoarthritic chondrocytes (OACs), leading to redifferentiation, restoring the synthesis of cartilage ECM components (Col2A1 and proteoglycans), and reducing the inflammatory and catabolic factors mediated by NF-kB (IL-1ß, IL-6, COX-2 and MMP-3), in addition to lowering cellular senescence in OACs, synovial and bone cells. Our in vitro results demonstrate the use of olive-derived polyphenols, such as oleuropein, as potentially effective therapeutic agents to improve chondrogenesis of hMSCs, to induce chondrocyte re-differentiation in OACs and clearing out senescent cells in joint tissues in order to prevent or stop the progression of the disease. Impact Journals 2020-08-03 /pmc/articles/PMC7485729/ /pubmed/32745074 http://dx.doi.org/10.18632/aging.103801 Text en Copyright © 2020 Varela-Eirín et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Priority Research Paper Varela-Eirín, Marta Carpintero-Fernández, Paula Sánchez-Temprano, Agustín Varela-Vázquez, Adrián Paíno, Carlos Luis Casado-Díaz, Antonio Continente, Alfonso Calañas Mato, Virginia Fonseca, Eduardo Kandouz, Mustapha Blanco, Alfonso Caeiro, José Ramón Mayán, María D. Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis |
title | Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis |
title_full | Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis |
title_fullStr | Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis |
title_full_unstemmed | Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis |
title_short | Senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis |
title_sort | senolytic activity of small molecular polyphenols from olive restores chondrocyte redifferentiation and promotes a pro-regenerative environment in osteoarthritis |
topic | Priority Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485729/ https://www.ncbi.nlm.nih.gov/pubmed/32745074 http://dx.doi.org/10.18632/aging.103801 |
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