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The P2X7 purinergic receptor in intervertebral disc degeneration
Mechanisms involved in the development of intervertebral disc (IVD) degeneration are only partially known, thus making the implementation of effective therapies very difficult. In this study, we investigated P2X7 purinergic receptor (P2X7R), NLRP3 inflammasome, and interleukin (IL)‐1β expression in...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9298011/ https://www.ncbi.nlm.nih.gov/pubmed/34668208 http://dx.doi.org/10.1002/jcp.30611 |
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author | Penolazzi, Letizia Bergamin, Leticia S. Lambertini, Elisabetta Poma, Valentina V. Sarti, Alba C. De Bonis, Pasquale Di Virgilio, Francesco Piva, Roberta |
author_facet | Penolazzi, Letizia Bergamin, Leticia S. Lambertini, Elisabetta Poma, Valentina V. Sarti, Alba C. De Bonis, Pasquale Di Virgilio, Francesco Piva, Roberta |
author_sort | Penolazzi, Letizia |
collection | PubMed |
description | Mechanisms involved in the development of intervertebral disc (IVD) degeneration are only partially known, thus making the implementation of effective therapies very difficult. In this study, we investigated P2X7 purinergic receptor (P2X7R), NLRP3 inflammasome, and interleukin (IL)‐1β expression in IVD specimens at different stages of disease progression, and during the in vitro dedifferentiation process of the primary cells derived thereof. We found that P2X7R, NLRP3, and IL‐1β expression was higher in the IVD samples at a more advanced stage of degeneration and in the expanded IVD cells in culture which partially recapitulated the in vivo degeneration process. In IVD cells, the P2X7R showed a striking nuclear localization, while NLRP3 was mainly cytoplasmic. Stimulation with the semiselective P2X7R agonist benzoyl ATP together with lipopolysaccharide treatment triggered P2X7R transfer to the cytoplasm and P2X7R/NLRP3 colocalization. Taken together, these findings support pathophysiological evidence that the degenerated disc is a highly inflamed microenvironment and highlight the P2X7R/NLRP3 axis as a suitable therapeutic target. The immunohistochemical analysis and the assessment of subcellular localization revealed a substantial expression of P2X7R also in normal disc tissue. This gives us the opportunity to contribute to the few studies performed in natively expressed human P2X7R so far, and to understand the possible physiological ATP‐mediated P2X7R homeostasis signaling. Therefore, collectively, our findings may offer a new perspective and pave the way for the exploration of a role of P2X7R‐mediated purinergic signaling in IVD metabolism that goes beyond its involvement in inflammation. |
format | Online Article Text |
id | pubmed-9298011 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92980112022-07-21 The P2X7 purinergic receptor in intervertebral disc degeneration Penolazzi, Letizia Bergamin, Leticia S. Lambertini, Elisabetta Poma, Valentina V. Sarti, Alba C. De Bonis, Pasquale Di Virgilio, Francesco Piva, Roberta J Cell Physiol Research Articles Mechanisms involved in the development of intervertebral disc (IVD) degeneration are only partially known, thus making the implementation of effective therapies very difficult. In this study, we investigated P2X7 purinergic receptor (P2X7R), NLRP3 inflammasome, and interleukin (IL)‐1β expression in IVD specimens at different stages of disease progression, and during the in vitro dedifferentiation process of the primary cells derived thereof. We found that P2X7R, NLRP3, and IL‐1β expression was higher in the IVD samples at a more advanced stage of degeneration and in the expanded IVD cells in culture which partially recapitulated the in vivo degeneration process. In IVD cells, the P2X7R showed a striking nuclear localization, while NLRP3 was mainly cytoplasmic. Stimulation with the semiselective P2X7R agonist benzoyl ATP together with lipopolysaccharide treatment triggered P2X7R transfer to the cytoplasm and P2X7R/NLRP3 colocalization. Taken together, these findings support pathophysiological evidence that the degenerated disc is a highly inflamed microenvironment and highlight the P2X7R/NLRP3 axis as a suitable therapeutic target. The immunohistochemical analysis and the assessment of subcellular localization revealed a substantial expression of P2X7R also in normal disc tissue. This gives us the opportunity to contribute to the few studies performed in natively expressed human P2X7R so far, and to understand the possible physiological ATP‐mediated P2X7R homeostasis signaling. Therefore, collectively, our findings may offer a new perspective and pave the way for the exploration of a role of P2X7R‐mediated purinergic signaling in IVD metabolism that goes beyond its involvement in inflammation. John Wiley and Sons Inc. 2021-10-19 2022-02 /pmc/articles/PMC9298011/ /pubmed/34668208 http://dx.doi.org/10.1002/jcp.30611 Text en © 2021 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Penolazzi, Letizia Bergamin, Leticia S. Lambertini, Elisabetta Poma, Valentina V. Sarti, Alba C. De Bonis, Pasquale Di Virgilio, Francesco Piva, Roberta The P2X7 purinergic receptor in intervertebral disc degeneration |
title | The P2X7 purinergic receptor in intervertebral disc degeneration |
title_full | The P2X7 purinergic receptor in intervertebral disc degeneration |
title_fullStr | The P2X7 purinergic receptor in intervertebral disc degeneration |
title_full_unstemmed | The P2X7 purinergic receptor in intervertebral disc degeneration |
title_short | The P2X7 purinergic receptor in intervertebral disc degeneration |
title_sort | p2x7 purinergic receptor in intervertebral disc degeneration |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9298011/ https://www.ncbi.nlm.nih.gov/pubmed/34668208 http://dx.doi.org/10.1002/jcp.30611 |
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