Experimental Mouse Model of Lumbar Ligamentum Flavum Hypertrophy
Lumbar spinal canal stenosis (LSCS) is one of the most common spinal disorders in elderly people, with the number of LSCS patients increasing due to the aging of the population. The ligamentum flavum (LF) is a spinal ligament located in the interior of the vertebral canal, and hypertrophy of the LF,...
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| creator | Saito, Takeyuki Yokota, Kazuya Kobayakawa, Kazu Hara, Masamitsu Kubota, Kensuke Harimaya, Katsumi Kawaguchi, Kenichi Hayashida, Mitsumasa Matsumoto, Yoshihiro Doi, Toshio Shiba, Keiichiro Nakashima, Yasuharu Okada, Seiji |
| description | Lumbar spinal canal stenosis (LSCS) is one of the most common spinal disorders in elderly people, with the number of LSCS patients increasing due to the aging of the population. The ligamentum flavum (LF) is a spinal ligament located in the interior of the vertebral canal, and hypertrophy of the LF, which causes the direct compression of the nerve roots and/or cauda equine, is a major cause of LSCS. Although there have been previous studies on LF hypertrophy, its pathomechanism remains unclear. The purpose of this study is to establish a relevant mouse model of LF hypertrophy and to examine disease-related factors. First, we focused on mechanical stress and developed a loading device for applying consecutive mechanical flexion-extension stress to the mouse LF. After 12 weeks of mechanical stress loading, we found that the LF thickness in the stress group was significantly increased in comparison to the control group. In addition, there were significant increases in the area of collagen fibers, the number of LF cells, and the gene expression of several fibrosis-related factors. However, in this mecnanical stress model, there was no macrophage infiltration, angiogenesis, or increase in the expression of transforming growth factor-β1 (TGF-β1), which are characteristic features of LF hypertrophy in LSCS patients. We therefore examined the influence of infiltrating macrophages on LF hypertrophy. After inducing macrophage infiltration by micro-injury to the mouse LF, we found excessive collagen synthesis in the injured site with the increased TGF-β1 expression at 2 weeks after injury, and further confirmed LF hypertrophy at 6 weeks after injury. Our findings demonstrate that mechanical stress is a causative factor for LF hypertrophy and strongly suggest the importance of macrophage infiltration in the progression of LF hypertrophy via the stimulation of collagen production. |
| doi_str_mv | 10.1371/journal.pone.0169717 |
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The ligamentum flavum (LF) is a spinal ligament located in the interior of the vertebral canal, and hypertrophy of the LF, which causes the direct compression of the nerve roots and/or cauda equine, is a major cause of LSCS. Although there have been previous studies on LF hypertrophy, its pathomechanism remains unclear. The purpose of this study is to establish a relevant mouse model of LF hypertrophy and to examine disease-related factors. First, we focused on mechanical stress and developed a loading device for applying consecutive mechanical flexion-extension stress to the mouse LF. After 12 weeks of mechanical stress loading, we found that the LF thickness in the stress group was significantly increased in comparison to the control group. In addition, there were significant increases in the area of collagen fibers, the number of LF cells, and the gene expression of several fibrosis-related factors. However, in this mecnanical stress model, there was no macrophage infiltration, angiogenesis, or increase in the expression of transforming growth factor-β1 (TGF-β1), which are characteristic features of LF hypertrophy in LSCS patients. We therefore examined the influence of infiltrating macrophages on LF hypertrophy. After inducing macrophage infiltration by micro-injury to the mouse LF, we found excessive collagen synthesis in the injured site with the increased TGF-β1 expression at 2 weeks after injury, and further confirmed LF hypertrophy at 6 weeks after injury. Our findings demonstrate that mechanical stress is a causative factor for LF hypertrophy and strongly suggest the importance of macrophage infiltration in the progression of LF hypertrophy via the stimulation of collagen production.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0169717</identifier><identifier>PMID: 28060908</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Aging ; Angiogenesis ; Animals ; Biology and Life Sciences ; Chemokines ; Collagen ; Collagen - metabolism ; Compression ; Development and progression ; Disease Models, Animal ; Female ; Fibers ; Fibrosis ; Gene Expression ; Genetic aspects ; Geriatrics ; Humans ; Hypertrophy ; Infiltration ; Injuries ; Kinases ; Ligamentum Flavum - diagnostic imaging ; Ligamentum Flavum - metabolism ; Ligamentum Flavum - pathology ; Lumbar Vertebrae ; Macrophages ; Macrophages - metabolism ; Medical research ; Medicine and Health Sciences ; Mice ; Mice, Transgenic ; Older people ; Patients ; Physical Sciences ; Physiological aspects ; Research and Analysis Methods ; RNA, Messenger - genetics ; Rodents ; Spinal cord injuries ; Stenosis ; Stress ; Stress, Mechanical ; Stresses ; Studies ; Surgery ; Transforming growth factor ; Transforming growth factor-b1 ; Transforming growth factors ; Vascular endothelial growth factor ; Vertebrae ; Young Adult</subject><ispartof>PloS one, 2017-01, Vol.12 (1), p.e0169717-e0169717</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Saito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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The ligamentum flavum (LF) is a spinal ligament located in the interior of the vertebral canal, and hypertrophy of the LF, which causes the direct compression of the nerve roots and/or cauda equine, is a major cause of LSCS. Although there have been previous studies on LF hypertrophy, its pathomechanism remains unclear. The purpose of this study is to establish a relevant mouse model of LF hypertrophy and to examine disease-related factors. First, we focused on mechanical stress and developed a loading device for applying consecutive mechanical flexion-extension stress to the mouse LF. After 12 weeks of mechanical stress loading, we found that the LF thickness in the stress group was significantly increased in comparison to the control group. In addition, there were significant increases in the area of collagen fibers, the number of LF cells, and the gene expression of several fibrosis-related factors. However, in this mecnanical stress model, there was no macrophage infiltration, angiogenesis, or increase in the expression of transforming growth factor-β1 (TGF-β1), which are characteristic features of LF hypertrophy in LSCS patients. We therefore examined the influence of infiltrating macrophages on LF hypertrophy. After inducing macrophage infiltration by micro-injury to the mouse LF, we found excessive collagen synthesis in the injured site with the increased TGF-β1 expression at 2 weeks after injury, and further confirmed LF hypertrophy at 6 weeks after injury. Our findings demonstrate that mechanical stress is a causative factor for LF hypertrophy and strongly suggest the importance of macrophage infiltration in the progression of LF hypertrophy via the stimulation of collagen production.</description><subject>Adult</subject><subject>Aged</subject><subject>Aging</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Biology and Life Sciences</subject><subject>Chemokines</subject><subject>Collagen</subject><subject>Collagen - metabolism</subject><subject>Compression</subject><subject>Development and progression</subject><subject>Disease Models, Animal</subject><subject>Female</subject><subject>Fibers</subject><subject>Fibrosis</subject><subject>Gene Expression</subject><subject>Genetic aspects</subject><subject>Geriatrics</subject><subject>Humans</subject><subject>Hypertrophy</subject><subject>Infiltration</subject><subject>Injuries</subject><subject>Kinases</subject><subject>Ligamentum Flavum - diagnostic 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Kenichi</au><au>Hayashida, Mitsumasa</au><au>Matsumoto, Yoshihiro</au><au>Doi, Toshio</au><au>Shiba, Keiichiro</au><au>Nakashima, Yasuharu</au><au>Okada, Seiji</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Experimental Mouse Model of Lumbar Ligamentum Flavum Hypertrophy</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-01-06</date><risdate>2017</risdate><volume>12</volume><issue>1</issue><spage>e0169717</spage><epage>e0169717</epage><pages>e0169717-e0169717</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Lumbar spinal canal stenosis (LSCS) is one of the most common spinal disorders in elderly people, with the number of LSCS patients increasing due to the aging of the population. The ligamentum flavum (LF) is a spinal ligament located in the interior of the vertebral canal, and hypertrophy of the LF, which causes the direct compression of the nerve roots and/or cauda equine, is a major cause of LSCS. Although there have been previous studies on LF hypertrophy, its pathomechanism remains unclear. The purpose of this study is to establish a relevant mouse model of LF hypertrophy and to examine disease-related factors. First, we focused on mechanical stress and developed a loading device for applying consecutive mechanical flexion-extension stress to the mouse LF. After 12 weeks of mechanical stress loading, we found that the LF thickness in the stress group was significantly increased in comparison to the control group. In addition, there were significant increases in the area of collagen fibers, the number of LF cells, and the gene expression of several fibrosis-related factors. However, in this mecnanical stress model, there was no macrophage infiltration, angiogenesis, or increase in the expression of transforming growth factor-β1 (TGF-β1), which are characteristic features of LF hypertrophy in LSCS patients. We therefore examined the influence of infiltrating macrophages on LF hypertrophy. After inducing macrophage infiltration by micro-injury to the mouse LF, we found excessive collagen synthesis in the injured site with the increased TGF-β1 expression at 2 weeks after injury, and further confirmed LF hypertrophy at 6 weeks after injury. Our findings demonstrate that mechanical stress is a causative factor for LF hypertrophy and strongly suggest the importance of macrophage infiltration in the progression of LF hypertrophy via the stimulation of collagen production.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28060908</pmid><doi>10.1371/journal.pone.0169717</doi><tpages>e0169717</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2017-01, Vol.12 (1), p.e0169717-e0169717 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1856128610 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Adult Aged Aging Angiogenesis Animals Biology and Life Sciences Chemokines Collagen Collagen - metabolism Compression Development and progression Disease Models, Animal Female Fibers Fibrosis Gene Expression Genetic aspects Geriatrics Humans Hypertrophy Infiltration Injuries Kinases Ligamentum Flavum - diagnostic imaging Ligamentum Flavum - metabolism Ligamentum Flavum - pathology Lumbar Vertebrae Macrophages Macrophages - metabolism Medical research Medicine and Health Sciences Mice Mice, Transgenic Older people Patients Physical Sciences Physiological aspects Research and Analysis Methods RNA, Messenger - genetics Rodents Spinal cord injuries Stenosis Stress Stress, Mechanical Stresses Studies Surgery Transforming growth factor Transforming growth factor-b1 Transforming growth factors Vascular endothelial growth factor Vertebrae Young Adult |
| title | Experimental Mouse Model of Lumbar Ligamentum Flavum Hypertrophy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T13%3A50%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Experimental%20Mouse%20Model%20of%20Lumbar%20Ligamentum%20Flavum%20Hypertrophy&rft.jtitle=PloS%20one&rft.au=Saito,%20Takeyuki&rft.date=2017-01-06&rft.volume=12&rft.issue=1&rft.spage=e0169717&rft.epage=e0169717&rft.pages=e0169717-e0169717&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0169717&rft_dat=%3Cgale_plos_%3EA476711100%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1856128610&rft_id=info:pmid/28060908&rft_galeid=A476711100&rft_doaj_id=oai_doaj_org_article_e9fbec609c744c64892eae46c4ea7b3d&rfr_iscdi=true |