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Modic type 2 changes are fibroinflammatory changes with complement system involvement adjacent to degenerated vertebral endplates
BACKGROUND: Vertebral endplate signal intensity changes visualized by magnetic resonance imaging termed Modic changes (MC) are highly prevalent in low back pain patients. Interconvertibility between the three MC subtypes (MC1, MC2, MC3) suggests different pathological stages. Histologically, granula...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10041382/ https://www.ncbi.nlm.nih.gov/pubmed/36994463 http://dx.doi.org/10.1002/jsp2.1237 |
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author | Heggli, Irina Laux, Christoph J. Mengis, Tamara Karol, Agnieszka Cornaz, Frédéric Herger, Nick Aradi‐Vegh, Borbala Widmer, Jonas Burkhard, Marco D. Farshad‐Amacker, Nadja A. Pfammatter, Sibylle Wolski, Witold E. Brunner, Florian Distler, Oliver Farshad, Mazda Dudli, Stefan |
author_facet | Heggli, Irina Laux, Christoph J. Mengis, Tamara Karol, Agnieszka Cornaz, Frédéric Herger, Nick Aradi‐Vegh, Borbala Widmer, Jonas Burkhard, Marco D. Farshad‐Amacker, Nadja A. Pfammatter, Sibylle Wolski, Witold E. Brunner, Florian Distler, Oliver Farshad, Mazda Dudli, Stefan |
author_sort | Heggli, Irina |
collection | PubMed |
description | BACKGROUND: Vertebral endplate signal intensity changes visualized by magnetic resonance imaging termed Modic changes (MC) are highly prevalent in low back pain patients. Interconvertibility between the three MC subtypes (MC1, MC2, MC3) suggests different pathological stages. Histologically, granulation tissue, fibrosis, and bone marrow edema are signs of inflammation in MC1 and MC2. However, different inflammatory infiltrates and amount of fatty marrow suggest distinct inflammatory processes in MC2. AIMS: The aims of this study were to investigate (i) the degree of bony (BEP) and cartilage endplate (CEP) degeneration in MC2, (ii) to identify inflammatory MC2 pathomechanisms, and (iii) to show that these marrow changes correlate with severity of endplate degeneration. METHODS: Pairs of axial biopsies (n = 58) spanning the entire vertebral body including both CEPs were collected from human cadaveric vertebrae with MC2. From one biopsy, the bone marrow directly adjacent to the CEP was analyzed with mass spectrometry. Differentially expressed proteins (DEPs) between MC2 and control were identified and bioinformatic enrichment analysis was performed. The other biopsy was processed for paraffin histology and BEP/CEP degenerations were scored. Endplate scores were correlated with DEPs. RESULTS: Endplates from MC2 were significantly more degenerated. Proteomic analysis revealed an activated complement system, increased expression of extracellular matrix proteins, angiogenic, and neurogenic factors in MC2 marrow. Endplate scores correlated with upregulated complement and neurogenic proteins. DISCUSSION: The inflammatory pathomechanisms in MC2 comprises activation of the complement system. Concurrent inflammation, fibrosis, angiogenesis, and neurogenesis indicate that MC2 is a chronic inflammation. Correlation of endplate damage with complement and neurogenic proteins suggest that complement system activation and neoinnervation may be linked to endplate damage. The endplate‐near marrow is the pathomechanistic site, because MC2 occur at locations with more endplate degeneration. CONCLUSION: MC2 are fibroinflammatory changes with complement system involvement which occur adjacent to damaged endplates. |
format | Online Article Text |
id | pubmed-10041382 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100413822023-03-28 Modic type 2 changes are fibroinflammatory changes with complement system involvement adjacent to degenerated vertebral endplates Heggli, Irina Laux, Christoph J. Mengis, Tamara Karol, Agnieszka Cornaz, Frédéric Herger, Nick Aradi‐Vegh, Borbala Widmer, Jonas Burkhard, Marco D. Farshad‐Amacker, Nadja A. Pfammatter, Sibylle Wolski, Witold E. Brunner, Florian Distler, Oliver Farshad, Mazda Dudli, Stefan JOR Spine Research Articles BACKGROUND: Vertebral endplate signal intensity changes visualized by magnetic resonance imaging termed Modic changes (MC) are highly prevalent in low back pain patients. Interconvertibility between the three MC subtypes (MC1, MC2, MC3) suggests different pathological stages. Histologically, granulation tissue, fibrosis, and bone marrow edema are signs of inflammation in MC1 and MC2. However, different inflammatory infiltrates and amount of fatty marrow suggest distinct inflammatory processes in MC2. AIMS: The aims of this study were to investigate (i) the degree of bony (BEP) and cartilage endplate (CEP) degeneration in MC2, (ii) to identify inflammatory MC2 pathomechanisms, and (iii) to show that these marrow changes correlate with severity of endplate degeneration. METHODS: Pairs of axial biopsies (n = 58) spanning the entire vertebral body including both CEPs were collected from human cadaveric vertebrae with MC2. From one biopsy, the bone marrow directly adjacent to the CEP was analyzed with mass spectrometry. Differentially expressed proteins (DEPs) between MC2 and control were identified and bioinformatic enrichment analysis was performed. The other biopsy was processed for paraffin histology and BEP/CEP degenerations were scored. Endplate scores were correlated with DEPs. RESULTS: Endplates from MC2 were significantly more degenerated. Proteomic analysis revealed an activated complement system, increased expression of extracellular matrix proteins, angiogenic, and neurogenic factors in MC2 marrow. Endplate scores correlated with upregulated complement and neurogenic proteins. DISCUSSION: The inflammatory pathomechanisms in MC2 comprises activation of the complement system. Concurrent inflammation, fibrosis, angiogenesis, and neurogenesis indicate that MC2 is a chronic inflammation. Correlation of endplate damage with complement and neurogenic proteins suggest that complement system activation and neoinnervation may be linked to endplate damage. The endplate‐near marrow is the pathomechanistic site, because MC2 occur at locations with more endplate degeneration. CONCLUSION: MC2 are fibroinflammatory changes with complement system involvement which occur adjacent to damaged endplates. John Wiley & Sons, Inc. 2022-12-23 /pmc/articles/PMC10041382/ /pubmed/36994463 http://dx.doi.org/10.1002/jsp2.1237 Text en © 2022 The Authors. JOR Spine published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Articles Heggli, Irina Laux, Christoph J. Mengis, Tamara Karol, Agnieszka Cornaz, Frédéric Herger, Nick Aradi‐Vegh, Borbala Widmer, Jonas Burkhard, Marco D. Farshad‐Amacker, Nadja A. Pfammatter, Sibylle Wolski, Witold E. Brunner, Florian Distler, Oliver Farshad, Mazda Dudli, Stefan Modic type 2 changes are fibroinflammatory changes with complement system involvement adjacent to degenerated vertebral endplates |
title | Modic type 2 changes are fibroinflammatory changes with complement system involvement adjacent to degenerated vertebral endplates |
title_full | Modic type 2 changes are fibroinflammatory changes with complement system involvement adjacent to degenerated vertebral endplates |
title_fullStr | Modic type 2 changes are fibroinflammatory changes with complement system involvement adjacent to degenerated vertebral endplates |
title_full_unstemmed | Modic type 2 changes are fibroinflammatory changes with complement system involvement adjacent to degenerated vertebral endplates |
title_short | Modic type 2 changes are fibroinflammatory changes with complement system involvement adjacent to degenerated vertebral endplates |
title_sort | modic type 2 changes are fibroinflammatory changes with complement system involvement adjacent to degenerated vertebral endplates |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10041382/ https://www.ncbi.nlm.nih.gov/pubmed/36994463 http://dx.doi.org/10.1002/jsp2.1237 |
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