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IL-6 is involved in thoracic ossification of the ligamentum flavum
Thoracic ossification of the ligamentum flavum (TOLF) is a heterotopic ossification of spinal ligaments. TOLF is the major cause of thoracic spinal canal stenosis and myelopathy, and its underlying mechanisms are not clear. Bone formation is a complex developmental process involving the differentiat...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337630/ https://www.ncbi.nlm.nih.gov/pubmed/35905126 http://dx.doi.org/10.1371/journal.pone.0272357 |
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author | Huang, Ann Yehong Shu, Li Chen, Zhongqiang Zhang, Chi |
author_facet | Huang, Ann Yehong Shu, Li Chen, Zhongqiang Zhang, Chi |
author_sort | Huang, Ann Yehong |
collection | PubMed |
description | Thoracic ossification of the ligamentum flavum (TOLF) is a heterotopic ossification of spinal ligaments. TOLF is the major cause of thoracic spinal canal stenosis and myelopathy, and its underlying mechanisms are not clear. Bone formation is a complex developmental process involving the differentiation of mesenchymal stem cells to osteoblasts, and regulated by BMP2, RUNX2, Osterix (OSX), etc. In this study, we continue to further characterize properties of TOLF. Our immunohistochemistry experiments showed that expressions of osteoblastic factors such as BMP2 and RUNX2 increased in TOLF. According to flow cytometry analysis the proportion of S phase of cell cycle in primary TOLF cells was 9% higher than the control. Alizarin red staining and ALP staining observations were consistent with immunohistochemistry results. It was also observed that inflammatory cytokine IL-6 level dramatically increased in the culture supernatant of primary TOLF cells. We propose the hypothesis that IL-6 is involved in TOLF. To testify the hypothesis, we examined the effect of IL-6. Our results showed that IL-6 was able to activate expressions of osteoblastic factors such as BMP2, RUNX2, OSX, OCN and ALP, and that expressions of cell proliferation factors cyclin D1 and cyclin C increased in the presence of IL-6. Moreover, IL-6-induced BMP2 expression was inhibited by p38 inhibitor SB203580, indicating that IL-6 regulated the osteogenic BMP2 activation through p38 MAPK pathway. These data suggest that IL-6 is involved in TOLF. |
format | Online Article Text |
id | pubmed-9337630 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-93376302022-07-30 IL-6 is involved in thoracic ossification of the ligamentum flavum Huang, Ann Yehong Shu, Li Chen, Zhongqiang Zhang, Chi PLoS One Research Article Thoracic ossification of the ligamentum flavum (TOLF) is a heterotopic ossification of spinal ligaments. TOLF is the major cause of thoracic spinal canal stenosis and myelopathy, and its underlying mechanisms are not clear. Bone formation is a complex developmental process involving the differentiation of mesenchymal stem cells to osteoblasts, and regulated by BMP2, RUNX2, Osterix (OSX), etc. In this study, we continue to further characterize properties of TOLF. Our immunohistochemistry experiments showed that expressions of osteoblastic factors such as BMP2 and RUNX2 increased in TOLF. According to flow cytometry analysis the proportion of S phase of cell cycle in primary TOLF cells was 9% higher than the control. Alizarin red staining and ALP staining observations were consistent with immunohistochemistry results. It was also observed that inflammatory cytokine IL-6 level dramatically increased in the culture supernatant of primary TOLF cells. We propose the hypothesis that IL-6 is involved in TOLF. To testify the hypothesis, we examined the effect of IL-6. Our results showed that IL-6 was able to activate expressions of osteoblastic factors such as BMP2, RUNX2, OSX, OCN and ALP, and that expressions of cell proliferation factors cyclin D1 and cyclin C increased in the presence of IL-6. Moreover, IL-6-induced BMP2 expression was inhibited by p38 inhibitor SB203580, indicating that IL-6 regulated the osteogenic BMP2 activation through p38 MAPK pathway. These data suggest that IL-6 is involved in TOLF. Public Library of Science 2022-07-29 /pmc/articles/PMC9337630/ /pubmed/35905126 http://dx.doi.org/10.1371/journal.pone.0272357 Text en © 2022 Huang et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Huang, Ann Yehong Shu, Li Chen, Zhongqiang Zhang, Chi IL-6 is involved in thoracic ossification of the ligamentum flavum |
title | IL-6 is involved in thoracic ossification of the ligamentum flavum |
title_full | IL-6 is involved in thoracic ossification of the ligamentum flavum |
title_fullStr | IL-6 is involved in thoracic ossification of the ligamentum flavum |
title_full_unstemmed | IL-6 is involved in thoracic ossification of the ligamentum flavum |
title_short | IL-6 is involved in thoracic ossification of the ligamentum flavum |
title_sort | il-6 is involved in thoracic ossification of the ligamentum flavum |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337630/ https://www.ncbi.nlm.nih.gov/pubmed/35905126 http://dx.doi.org/10.1371/journal.pone.0272357 |
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