Microtubule destabilization caused by silicate via HDAC6 activation contributes to autophagic dysfunction in bone mesenchymal stem cells
Identifieur interne : 000211 ( Pmc/Curation ); précédent : 000210; suivant : 000212Microtubule destabilization caused by silicate via HDAC6 activation contributes to autophagic dysfunction in bone mesenchymal stem cells
Auteurs : Zheng Li ; Shuhao Liu ; Tengfei Fu ; Yi Peng ; Jian ZhangSource :
- Stem Cell Research & Therapy [ 1757-6512 ] ; 2019.
Abstract
Silicon-modified biomaterials have been extensively studied in bone tissue engineering. In recent years, the toxicity of silicon-doped biomaterials has gradually attracted attention but requires further elucidation. This study was designed to explore whether high-dose silicate can induce a cytotoxicity effect in bone mesenchymal stem cells (BMSCs) and the role of autophagy in its cytotoxicity and mechanism.
Morphologic changes and cell viability of BMSCs were detected after different doses of silicate exposure. Autophagic proteins (LC3, p62), LC3 turnover assay, and RFP-GFP-LC3 assay were applied to detect the changes of autophagic flux following silicate treatment. Furthermore, to identify the potential mechanism of autophagic dysfunction, we tested the acetyl-α-tubulin protein level and histone deacetylase 6 (HDAC6) activity after high-dose silicate exposure as well as the changes in microtubule and autophagic activity after HDAC6 siRNA was applied.
It was found that a high dose of silicate could induce a decrease in cell viability; LC3-II and p62 simultaneously increased after high-dose silicate exposure. A high concentration of silicate could induce autophagic dysfunction and cause autophagosomes to accumulate via microtubule destabilization. Results showed that acetyl-α-tubulin decreased significantly with high-dose silicate treatment, and inhibition of HDAC6 activity can restore microtubule structure and autophagic flux.
Microtubule destabilization caused by a high concentration of silicate via HDAC6 activation contributed to autophagic dysfunction in BMSCs, and inhibition of HDAC6 exerted a cytoprotection effect through restoration of the microtubule structure and autophagic flux.
Url:
DOI: 10.1186/s13287-019-1441-4
PubMed: 31775910
PubMed Central: 6880487
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Microtubule destabilization caused by silicate via HDAC6 activation contributes to autophagic dysfunction in bone mesenchymal stem cells</title>
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<author><name sortKey="Zhang, Jian" sort="Zhang, Jian" uniqKey="Zhang J" first="Jian" last="Zhang">Jian Zhang</name>
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<series><title level="j">Stem Cell Research & Therapy</title>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p id="Par1">Silicon-modified biomaterials have been extensively studied in bone tissue engineering. In recent years, the toxicity of silicon-doped biomaterials has gradually attracted attention but requires further elucidation. This study was designed to explore whether high-dose silicate can induce a cytotoxicity effect in bone mesenchymal stem cells (BMSCs) and the role of autophagy in its cytotoxicity and mechanism.</p>
</sec>
<sec><title>Methods</title>
<p id="Par2">Morphologic changes and cell viability of BMSCs were detected after different doses of silicate exposure. Autophagic proteins (LC3, p62), LC3 turnover assay, and RFP-GFP-LC3 assay were applied to detect the changes of autophagic flux following silicate treatment. Furthermore, to identify the potential mechanism of autophagic dysfunction, we tested the acetyl-α-tubulin protein level and histone deacetylase 6 (HDAC6) activity after high-dose silicate exposure as well as the changes in microtubule and autophagic activity after HDAC6 siRNA was applied.</p>
</sec>
<sec><title>Results</title>
<p id="Par3">It was found that a high dose of silicate could induce a decrease in cell viability; LC3-II and p62 simultaneously increased after high-dose silicate exposure. A high concentration of silicate could induce autophagic dysfunction and cause autophagosomes to accumulate via microtubule destabilization. Results showed that acetyl-α-tubulin decreased significantly with high-dose silicate treatment, and inhibition of HDAC6 activity can restore microtubule structure and autophagic flux.</p>
</sec>
<sec><title>Conclusions</title>
<p id="Par4">Microtubule destabilization caused by a high concentration of silicate via HDAC6 activation contributed to autophagic dysfunction in BMSCs, and inhibition of HDAC6 exerted a cytoprotection effect through restoration of the microtubule structure and autophagic flux.</p>
</sec>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Stem Cell Res Ther</journal-id>
<journal-id journal-id-type="iso-abbrev">Stem Cell Res Ther</journal-id>
<journal-title-group><journal-title>Stem Cell Research & Therapy</journal-title>
</journal-title-group>
<issn pub-type="epub">1757-6512</issn>
<publisher><publisher-name>BioMed Central</publisher-name>
<publisher-loc>London</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">31775910</article-id>
<article-id pub-id-type="pmc">6880487</article-id>
<article-id pub-id-type="publisher-id">1441</article-id>
<article-id pub-id-type="doi">10.1186/s13287-019-1441-4</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research</subject>
</subj-group>
</article-categories>
<title-group><article-title>Microtubule destabilization caused by silicate via HDAC6 activation contributes to autophagic dysfunction in bone mesenchymal stem cells</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" equal-contrib="yes"><name><surname>Li</surname>
<given-names>Zheng</given-names>
</name>
<xref ref-type="aff" rid="Aff1"></xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Liu</surname>
<given-names>Shuhao</given-names>
</name>
<xref ref-type="aff" rid="Aff1"></xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Fu</surname>
<given-names>Tengfei</given-names>
</name>
<xref ref-type="aff" rid="Aff1"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Peng</surname>
<given-names>Yi</given-names>
</name>
<xref ref-type="aff" rid="Aff1"></xref>
</contrib>
<contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-1475-2276</contrib-id>
<name><surname>Zhang</surname>
<given-names>Jian</given-names>
</name>
<address><phone>+8617521188073</phone>
<email>zhangjianzsyy@126.com</email>
</address>
<xref ref-type="aff" rid="Aff1"></xref>
</contrib>
<aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1755 3939</institution-id>
<institution-id institution-id-type="GRID">grid.413087.9</institution-id>
<institution>Department of Orthopaedics,</institution>
<institution>Zhongshan Hospital of Fudan University,</institution>
</institution-wrap>
180 Fenglin Road, Shanghai, China</aff>
</contrib-group>
<pub-date pub-type="epub"><day>27</day>
<month>11</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>27</day>
<month>11</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="collection"><year>2019</year>
</pub-date>
<volume>10</volume>
<elocation-id>351</elocation-id>
<history><date date-type="received"><day>11</day>
<month>5</month>
<year>2019</year>
</date>
<date date-type="rev-recd"><day>1</day>
<month>9</month>
<year>2019</year>
</date>
<date date-type="accepted"><day>3</day>
<month>10</month>
<year>2019</year>
</date>
</history>
<permissions><copyright-statement>© The Author(s). 2019</copyright-statement>
<license license-type="OpenAccess"><license-p><bold>Open Access</bold>
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>
) applies to the data made available in this article, unless otherwise stated.</license-p>
</license>
</permissions>
<abstract id="Abs1"><sec><title>Background</title>
<p id="Par1">Silicon-modified biomaterials have been extensively studied in bone tissue engineering. In recent years, the toxicity of silicon-doped biomaterials has gradually attracted attention but requires further elucidation. This study was designed to explore whether high-dose silicate can induce a cytotoxicity effect in bone mesenchymal stem cells (BMSCs) and the role of autophagy in its cytotoxicity and mechanism.</p>
</sec>
<sec><title>Methods</title>
<p id="Par2">Morphologic changes and cell viability of BMSCs were detected after different doses of silicate exposure. Autophagic proteins (LC3, p62), LC3 turnover assay, and RFP-GFP-LC3 assay were applied to detect the changes of autophagic flux following silicate treatment. Furthermore, to identify the potential mechanism of autophagic dysfunction, we tested the acetyl-α-tubulin protein level and histone deacetylase 6 (HDAC6) activity after high-dose silicate exposure as well as the changes in microtubule and autophagic activity after HDAC6 siRNA was applied.</p>
</sec>
<sec><title>Results</title>
<p id="Par3">It was found that a high dose of silicate could induce a decrease in cell viability; LC3-II and p62 simultaneously increased after high-dose silicate exposure. A high concentration of silicate could induce autophagic dysfunction and cause autophagosomes to accumulate via microtubule destabilization. Results showed that acetyl-α-tubulin decreased significantly with high-dose silicate treatment, and inhibition of HDAC6 activity can restore microtubule structure and autophagic flux.</p>
</sec>
<sec><title>Conclusions</title>
<p id="Par4">Microtubule destabilization caused by a high concentration of silicate via HDAC6 activation contributed to autophagic dysfunction in BMSCs, and inhibition of HDAC6 exerted a cytoprotection effect through restoration of the microtubule structure and autophagic flux.</p>
</sec>
</abstract>
<kwd-group xml:lang="en"><title>Keywords</title>
<kwd>BMSCs</kwd>
<kwd>Silicate</kwd>
<kwd>Autophagic flux</kwd>
<kwd>Microtubule</kwd>
<kwd>HDAC6</kwd>
</kwd-group>
<funding-group><award-group><funding-source><institution> Key Project of Natural Science Foundation of China</institution>
</funding-source>
<award-id>31330028</award-id>
<principal-award-recipient><name><surname>Zhang</surname>
<given-names>Jian</given-names>
</name>
</principal-award-recipient>
</award-group>
</funding-group>
<custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name>
<meta-value>© The Author(s) 2019</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
</pmc>
</record>
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