Microtubule stabilization promotes the synthesis of type 2 collagen in nucleus pulposus cell by activating hippo-yap pathway
Intervertebral disc degeneration (IDD) is the cardinal pathological mechanism that underlies low back pain. Mechanical stress of the intervertebral disc may result in a change in nucleus pulposus cells state, matrix degradation, and degeneration of the disc. Microtubules, which are components of the...
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| Published in | Frontiers in pharmacology Vol. 14; p. 1102318 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
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| Abstract | Intervertebral disc degeneration (IDD) is the cardinal pathological mechanism that underlies low back pain. Mechanical stress of the intervertebral disc may result in a change in nucleus pulposus cells state, matrix degradation, and degeneration of the disc. Microtubules, which are components of the cytoskeleton, are involved in driving or regulating signal pathways, which sense and transmit mechano-transduction. Microtubule and the related proteins play an important role in the development of many diseases, while little is known about the role of microtubules in nucleus pulposus cells. Researchers have found that type II collagen (COL2) expression is promoted by microtubule stabilization in synovial mesenchymal stem cells. In this study, we demonstrated that microtubule stabilization promotes the expression of COL2 in nucleus pulposus cells. Stabilized microtubules stimulating Hippo signaling pathway, inhibiting YAP protein expression and activity. In addition, microtubules stabilization promotes the expression of COL2 and alleviates disc degeneration in rats. In summary, our study for the first time, identifies microtubule as a promising therapeutic target for IDD, up-regulating the synthesis of COL2
via
Hippo-Yap pathway. Our findings may provide new insights into the etiologies and pathology for IDD, further, targeting of microtubule acetylation may be an effective strategy for the treatment of IDD. |
|---|---|
| AbstractList | Intervertebral disc degeneration (IDD) is the cardinal pathological mechanism that underlies low back pain. Mechanical stress of the intervertebral disc may result in a change in nucleus pulposus cells state, matrix degradation, and degeneration of the disc. Microtubules, which are components of the cytoskeleton, are involved in driving or regulating signal pathways, which sense and transmit mechano-transduction. Microtubule and the related proteins play an important role in the development of many diseases, while little is known about the role of microtubules in nucleus pulposus cells. Researchers have found that type II collagen (COL2) expression is promoted by microtubule stabilization in synovial mesenchymal stem cells. In this study, we demonstrated that microtubule stabilization promotes the expression of COL2 in nucleus pulposus cells. Stabilized microtubules stimulating Hippo signaling pathway, inhibiting YAP protein expression and activity. In addition, microtubules stabilization promotes the expression of COL2 and alleviates disc degeneration in rats. In summary, our study for the first time, identifies microtubule as a promising therapeutic target for IDD, up-regulating the synthesis of COL2 via Hippo-Yap pathway. Our findings may provide new insights into the etiologies and pathology for IDD, further, targeting of microtubule acetylation may be an effective strategy for the treatment of IDD.Intervertebral disc degeneration (IDD) is the cardinal pathological mechanism that underlies low back pain. Mechanical stress of the intervertebral disc may result in a change in nucleus pulposus cells state, matrix degradation, and degeneration of the disc. Microtubules, which are components of the cytoskeleton, are involved in driving or regulating signal pathways, which sense and transmit mechano-transduction. Microtubule and the related proteins play an important role in the development of many diseases, while little is known about the role of microtubules in nucleus pulposus cells. Researchers have found that type II collagen (COL2) expression is promoted by microtubule stabilization in synovial mesenchymal stem cells. In this study, we demonstrated that microtubule stabilization promotes the expression of COL2 in nucleus pulposus cells. Stabilized microtubules stimulating Hippo signaling pathway, inhibiting YAP protein expression and activity. In addition, microtubules stabilization promotes the expression of COL2 and alleviates disc degeneration in rats. In summary, our study for the first time, identifies microtubule as a promising therapeutic target for IDD, up-regulating the synthesis of COL2 via Hippo-Yap pathway. Our findings may provide new insights into the etiologies and pathology for IDD, further, targeting of microtubule acetylation may be an effective strategy for the treatment of IDD. Intervertebral disc degeneration (IDD) is the cardinal pathological mechanism that underlies low back pain. Mechanical stress of the intervertebral disc may result in a change in nucleus pulposus cells state, matrix degradation, and degeneration of the disc. Microtubules, which are components of the cytoskeleton, are involved in driving or regulating signal pathways, which sense and transmit mechano-transduction. Microtubule and the related proteins play an important role in the development of many diseases, while little is known about the role of microtubules in nucleus pulposus cells. Researchers have found that type II collagen (COL2) expression is promoted by microtubule stabilization in synovial mesenchymal stem cells. In this study, we demonstrated that microtubule stabilization promotes the expression of COL2 in nucleus pulposus cells. Stabilized microtubules stimulating Hippo signaling pathway, inhibiting YAP protein expression and activity. In addition, microtubules stabilization promotes the expression of COL2 and alleviates disc degeneration in rats. In summary, our study for the first time, identifies microtubule as a promising therapeutic target for IDD, up-regulating the synthesis of COL2 via Hippo-Yap pathway. Our findings may provide new insights into the etiologies and pathology for IDD, further, targeting of microtubule acetylation may be an effective strategy for the treatment of IDD. Intervertebral disc degeneration (IDD) is the cardinal pathological mechanism that underlies low back pain. Mechanical stress of the intervertebral disc may result in a change in nucleus pulposus cells state, matrix degradation, and degeneration of the disc. Microtubules, which are components of the cytoskeleton, are involved in driving or regulating signal pathways, which sense and transmit mechano-transduction. Microtubule and the related proteins play an important role in the development of many diseases, while little is known about the role of microtubules in nucleus pulposus cells. Researchers have found that type II collagen (COL2) expression is promoted by microtubule stabilization in synovial mesenchymal stem cells. In this study, we demonstrated that microtubule stabilization promotes the expression of COL2 in nucleus pulposus cells. Stabilized microtubules stimulating Hippo signaling pathway, inhibiting YAP protein expression and activity. In addition, microtubules stabilization promotes the expression of COL2 and alleviates disc degeneration in rats. In summary, our study for the first time, identifies microtubule as a promising therapeutic target for IDD, up-regulating the synthesis of COL2 Hippo-Yap pathway. Our findings may provide new insights into the etiologies and pathology for IDD, further, targeting of microtubule acetylation may be an effective strategy for the treatment of IDD. Intervertebral disc degeneration (IDD) is the cardinal pathological mechanism that underlies low back pain. Mechanical stress of the intervertebral disc may result in a change in nucleus pulposus cells state, matrix degradation, and degeneration of the disc. Microtubules, which are components of the cytoskeleton, are involved in driving or regulating signal pathways, which sense and transmit mechano-transduction. Microtubule and the related proteins play an important role in the development of many diseases, while little is known about the role of microtubules in nucleus pulposus cells. Researchers have found that type II collagen (COL2) expression is promoted by microtubule stabilization in synovial mesenchymal stem cells. In this study, we demonstrated that microtubule stabilization promotes the expression of COL2 in nucleus pulposus cells. Stabilized microtubules stimulating Hippo signaling pathway, inhibiting YAP protein expression and activity. In addition, microtubules stabilization promotes the expression of COL2 and alleviates disc degeneration in rats. In summary, our study for the first time, identifies microtubule as a promising therapeutic target for IDD, up-regulating the synthesis of COL2 via Hippo-Yap pathway. Our findings may provide new insights into the etiologies and pathology for IDD, further, targeting of microtubule acetylation may be an effective strategy for the treatment of IDD. |
| Author | Zhang, Xin Bao, Hongda Shu, Shibin Qiu, Yong Feng, Zhenhua Zhu, Zezhang |
| AuthorAffiliation | Division of Spine Surgery , Department of Orthopedic Surgery , Nanjing Drum Tower Hospital , The Affiliated Hospital of Nanjing University Medical School , Nanjing , China |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/36778003$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1247/csf.21.317 10.1002/art.34566 10.3389/fcell.2021.748804 10.1016/j.ceb.2014.09.003 10.1038/ncomms6370 10.1089/scd.2012.0685 10.18632/oncotarget.23299 10.1074/jbc.M806245200 10.1016/j.acthis.2021.151770 10.1038/nrg2774 10.1038/ncb1001-913 10.1371/journal.pone.0062411 10.1016/j.joca.2015.08.014 10.1097/BRS.0b013e318158cb61 10.1002/jemt.1070280503 10.1007/s12035-016-0188-5 10.1038/nmat4396 10.1016/j.redox.2018.09.006 10.1101/cshperspect.a022608 10.1002/jor.20867 10.1038/ncb2756 10.1038/s41418-020-0597-x 10.1016/j.joca.2011.04.005 10.1038/nature10137 10.1038/cddiscovery.2016.107 10.1016/j.mcn.2010.12.011 10.1039/c7nr05818g 10.1371/journal.pone.0033147 10.1096/fj.201902838R 10.1038/nrm1260 10.1101/gad.274027.115 10.1016/j.ajpath.2013.11.010 10.1016/j.cub.2017.10.044 10.1126/science.aai8764 10.1038/s41467-019-10207-y 10.1002/(SICI)1097-0177(199907)215:3<179::AID-AJA1>3.0.CO;2-Q 10.1093/brain/awt153 10.1097/BRS.0b013e31817c64a9 10.1016/j.cell.2012.06.037 10.1016/j.matbio.2003.11.008 10.1016/j.joca.2014.05.011 10.1038/421230a 10.1038/s41580-021-00399-x 10.1002/cbin.11851 10.1016/j.cell.2014.03.061 10.1083/jcb.200601060 |
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| Copyright | Copyright © 2023 Zhang, Shu, Feng, Qiu, Bao and Zhu. Copyright © 2023 Zhang, Shu, Feng, Qiu, Bao and Zhu. 2023 Zhang, Shu, Feng, Qiu, Bao and Zhu |
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| Keywords | intervertebral disc degeneration mechanical stress intervertebral disc nucleus pulposus microtubule stabilization |
| Language | English |
| License | Copyright © 2023 Zhang, Shu, Feng, Qiu, Bao and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
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| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Xuewen Kang, Lanzhou University Second Hospital, China This article was submitted to Integrative and Regenerative Pharmacology, a section of the journal Frontiers in Pharmacology Reviewed by: Feng-Juan Lyu, South China University of Technology, China Yu Song, Huazhong University of Science and Technology, China Edited by: Chen-he Zhou, Zhejiang University, China |
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| StartPage | 1102318 |
| SubjectTerms | intervertebral disc intervertebral disc degeneration mechanical stress microtubule stabilization nucleus pulposus Pharmacology |
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| Title | Microtubule stabilization promotes the synthesis of type 2 collagen in nucleus pulposus cell by activating hippo-yap pathway |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/36778003 https://www.proquest.com/docview/2775955685 https://pubmed.ncbi.nlm.nih.gov/PMC9909034 https://doaj.org/article/ce53c2db8a274cd6952d89a7f8c158e5 |
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