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The Role of Panx3 in Age-Associated and Injury-Induced Intervertebral Disc Degeneration
Pannexin 3 (Panx3) is a mechanosensitive, channel-forming glycoprotein implicated in the progression of post-traumatic osteoarthritis. Despite evidence for Panx3 expression in the intervertebral disc (IVD), its function in this cartilaginous joint structure remained unknown. Using Panx3 knockout mic...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865929/ https://www.ncbi.nlm.nih.gov/pubmed/33499145 http://dx.doi.org/10.3390/ijms22031080 |
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author | Serjeant, Meaghan Moon, Paxton M. Quinonez, Diana Penuela, Silvia Beier, Frank Séguin, Cheryle A. |
author_facet | Serjeant, Meaghan Moon, Paxton M. Quinonez, Diana Penuela, Silvia Beier, Frank Séguin, Cheryle A. |
author_sort | Serjeant, Meaghan |
collection | PubMed |
description | Pannexin 3 (Panx3) is a mechanosensitive, channel-forming glycoprotein implicated in the progression of post-traumatic osteoarthritis. Despite evidence for Panx3 expression in the intervertebral disc (IVD), its function in this cartilaginous joint structure remained unknown. Using Panx3 knockout mice, this study investigated the role of Panx3 in age-associated IVD degeneration and degeneration induced by annulus fibrosus (AF) needle puncture. Loss of Panx3 did not significantly impact the progression of age-associated histopathological IVD degeneration; however, loss of Panx3 was associated with decreased gene expression of Acan, Col1a1, Mmp13 and Runx2 and altered localization of COLX in the IVD at 19 months-of-age. Following IVD injury in the caudal spine, histological analysis of wild-type mice revealed clusters of hypertrophic cells in the AF associated with increased pericellular proteoglycan accumulation, disruptions in lamellar organization and increased lamellar thickness. In Panx3 knockout mice, hypertrophic AF cells were rarely detected and AF structure was largely preserved post-injury. Interestingly, uninjured IVDs adjacent to the site of injury more frequently showed evidence of early nucleus pulposus degeneration in Panx3 knockout mice but remained healthy in wild-type mice. These findings suggest a role for Panx3 in mediating the adaptive cellular responses to altered mechanical stress in the IVD, which may buffer aberrant loads transferred to adjacent motion segments. |
format | Online Article Text |
id | pubmed-7865929 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-78659292021-02-07 The Role of Panx3 in Age-Associated and Injury-Induced Intervertebral Disc Degeneration Serjeant, Meaghan Moon, Paxton M. Quinonez, Diana Penuela, Silvia Beier, Frank Séguin, Cheryle A. Int J Mol Sci Article Pannexin 3 (Panx3) is a mechanosensitive, channel-forming glycoprotein implicated in the progression of post-traumatic osteoarthritis. Despite evidence for Panx3 expression in the intervertebral disc (IVD), its function in this cartilaginous joint structure remained unknown. Using Panx3 knockout mice, this study investigated the role of Panx3 in age-associated IVD degeneration and degeneration induced by annulus fibrosus (AF) needle puncture. Loss of Panx3 did not significantly impact the progression of age-associated histopathological IVD degeneration; however, loss of Panx3 was associated with decreased gene expression of Acan, Col1a1, Mmp13 and Runx2 and altered localization of COLX in the IVD at 19 months-of-age. Following IVD injury in the caudal spine, histological analysis of wild-type mice revealed clusters of hypertrophic cells in the AF associated with increased pericellular proteoglycan accumulation, disruptions in lamellar organization and increased lamellar thickness. In Panx3 knockout mice, hypertrophic AF cells were rarely detected and AF structure was largely preserved post-injury. Interestingly, uninjured IVDs adjacent to the site of injury more frequently showed evidence of early nucleus pulposus degeneration in Panx3 knockout mice but remained healthy in wild-type mice. These findings suggest a role for Panx3 in mediating the adaptive cellular responses to altered mechanical stress in the IVD, which may buffer aberrant loads transferred to adjacent motion segments. MDPI 2021-01-22 /pmc/articles/PMC7865929/ /pubmed/33499145 http://dx.doi.org/10.3390/ijms22031080 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Serjeant, Meaghan Moon, Paxton M. Quinonez, Diana Penuela, Silvia Beier, Frank Séguin, Cheryle A. The Role of Panx3 in Age-Associated and Injury-Induced Intervertebral Disc Degeneration |
title | The Role of Panx3 in Age-Associated and Injury-Induced Intervertebral Disc Degeneration |
title_full | The Role of Panx3 in Age-Associated and Injury-Induced Intervertebral Disc Degeneration |
title_fullStr | The Role of Panx3 in Age-Associated and Injury-Induced Intervertebral Disc Degeneration |
title_full_unstemmed | The Role of Panx3 in Age-Associated and Injury-Induced Intervertebral Disc Degeneration |
title_short | The Role of Panx3 in Age-Associated and Injury-Induced Intervertebral Disc Degeneration |
title_sort | role of panx3 in age-associated and injury-induced intervertebral disc degeneration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865929/ https://www.ncbi.nlm.nih.gov/pubmed/33499145 http://dx.doi.org/10.3390/ijms22031080 |
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