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Advanced glycation end products cause RAGE‐dependent annulus fibrosus collagen disruption and loss identified using in situ second harmonic generation imaging in mice intervertebral disk in vivo and in organ culture models
Aging and diabetes are associated with increased low‐back pain and intervertebral disk (IVD) degeneration yet causal mechanisms remain uncertain. Advanced glycation end products (AGEs), which accumulate in IVDs from aging and are implicated in diabetes‐related disorders, alter collagen and induce pr...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770195/ https://www.ncbi.nlm.nih.gov/pubmed/33392460 http://dx.doi.org/10.1002/jsp2.1126 |
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author | Hoy, Robert C. D'Erminio, Danielle N. Krishnamoorthy, Divya Natelson, Devorah M. Laudier, Damien M. Illien‐Jünger, Svenja Iatridis, James C. |
author_facet | Hoy, Robert C. D'Erminio, Danielle N. Krishnamoorthy, Divya Natelson, Devorah M. Laudier, Damien M. Illien‐Jünger, Svenja Iatridis, James C. |
author_sort | Hoy, Robert C. |
collection | PubMed |
description | Aging and diabetes are associated with increased low‐back pain and intervertebral disk (IVD) degeneration yet causal mechanisms remain uncertain. Advanced glycation end products (AGEs), which accumulate in IVDs from aging and are implicated in diabetes‐related disorders, alter collagen and induce proinflammatory conditions. A need exists for methods that assess IVD collagen quality and degradation in order to better characterize specific structural changes in IVDs due to AGE accumulation and to identify roles for the receptor for AGEs (RAGE). We used multiphoton microscopy with second harmonic generation (SHG), collagen‐hybridizing peptide (CHP), and image analysis methods to characterize effects of AGEs and RAGE on collagen quality and quantity in IVD annulus fibrosus (AF). First, we used SHG imaging on thin sections with an in vivo dietary mouse model and determined that high‐AGE (H‐AGE) diets increased AF fibril disruption and collagen degradation resulting in decreased total collagen content, suggesting an early degenerative cascade. Next, we used in situ SHG imaging with an ex vivo IVD organ culture model of AGE challenge on wild type and RAGE‐knockout (RAGE‐KO) mice and determined that early degenerative changes to collagen quality and degradation were RAGE dependent. We conclude that AGE accumulation leads to RAGE‐dependent collagen disruption in the AF and can initiate molecular and tissue level collagen disruption. Furthermore, SHG and CHP analyzes were sensitive to collagenous alterations at multiple hierarchical levels due to AGE and may be useful in identifying additional contributors to collagen damage in IVD degeneration processes. |
format | Online Article Text |
id | pubmed-7770195 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77701952020-12-31 Advanced glycation end products cause RAGE‐dependent annulus fibrosus collagen disruption and loss identified using in situ second harmonic generation imaging in mice intervertebral disk in vivo and in organ culture models Hoy, Robert C. D'Erminio, Danielle N. Krishnamoorthy, Divya Natelson, Devorah M. Laudier, Damien M. Illien‐Jünger, Svenja Iatridis, James C. JOR Spine Special Issue PSRS Conference 2019 Aging and diabetes are associated with increased low‐back pain and intervertebral disk (IVD) degeneration yet causal mechanisms remain uncertain. Advanced glycation end products (AGEs), which accumulate in IVDs from aging and are implicated in diabetes‐related disorders, alter collagen and induce proinflammatory conditions. A need exists for methods that assess IVD collagen quality and degradation in order to better characterize specific structural changes in IVDs due to AGE accumulation and to identify roles for the receptor for AGEs (RAGE). We used multiphoton microscopy with second harmonic generation (SHG), collagen‐hybridizing peptide (CHP), and image analysis methods to characterize effects of AGEs and RAGE on collagen quality and quantity in IVD annulus fibrosus (AF). First, we used SHG imaging on thin sections with an in vivo dietary mouse model and determined that high‐AGE (H‐AGE) diets increased AF fibril disruption and collagen degradation resulting in decreased total collagen content, suggesting an early degenerative cascade. Next, we used in situ SHG imaging with an ex vivo IVD organ culture model of AGE challenge on wild type and RAGE‐knockout (RAGE‐KO) mice and determined that early degenerative changes to collagen quality and degradation were RAGE dependent. We conclude that AGE accumulation leads to RAGE‐dependent collagen disruption in the AF and can initiate molecular and tissue level collagen disruption. Furthermore, SHG and CHP analyzes were sensitive to collagenous alterations at multiple hierarchical levels due to AGE and may be useful in identifying additional contributors to collagen damage in IVD degeneration processes. John Wiley & Sons, Inc. 2020-09-21 /pmc/articles/PMC7770195/ /pubmed/33392460 http://dx.doi.org/10.1002/jsp2.1126 Text en © 2020 The Authors. JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Special Issue PSRS Conference 2019 Hoy, Robert C. D'Erminio, Danielle N. Krishnamoorthy, Divya Natelson, Devorah M. Laudier, Damien M. Illien‐Jünger, Svenja Iatridis, James C. Advanced glycation end products cause RAGE‐dependent annulus fibrosus collagen disruption and loss identified using in situ second harmonic generation imaging in mice intervertebral disk in vivo and in organ culture models |
title | Advanced glycation end products cause RAGE‐dependent annulus fibrosus collagen disruption and loss identified using in situ second harmonic generation imaging in mice intervertebral disk in vivo and in organ culture models |
title_full | Advanced glycation end products cause RAGE‐dependent annulus fibrosus collagen disruption and loss identified using in situ second harmonic generation imaging in mice intervertebral disk in vivo and in organ culture models |
title_fullStr | Advanced glycation end products cause RAGE‐dependent annulus fibrosus collagen disruption and loss identified using in situ second harmonic generation imaging in mice intervertebral disk in vivo and in organ culture models |
title_full_unstemmed | Advanced glycation end products cause RAGE‐dependent annulus fibrosus collagen disruption and loss identified using in situ second harmonic generation imaging in mice intervertebral disk in vivo and in organ culture models |
title_short | Advanced glycation end products cause RAGE‐dependent annulus fibrosus collagen disruption and loss identified using in situ second harmonic generation imaging in mice intervertebral disk in vivo and in organ culture models |
title_sort | advanced glycation end products cause rage‐dependent annulus fibrosus collagen disruption and loss identified using in situ second harmonic generation imaging in mice intervertebral disk in vivo and in organ culture models |
topic | Special Issue PSRS Conference 2019 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770195/ https://www.ncbi.nlm.nih.gov/pubmed/33392460 http://dx.doi.org/10.1002/jsp2.1126 |
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