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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Involvement of ERCC1 in the Pathogenesis of Osteoarthritis Through the Modulation of Apoptosis and Cellular Senescence</title><author><name sortKey="Takayama, Koji" sort="Takayama, Koji" uniqKey="Takayama K" first="Koji" last="Takayama">Koji Takayama</name><affiliation><nlm:aff id="A1">Stem Cell Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15219</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</nlm:aff></affiliation></author><author><name sortKey="Kawakami, Yohei" sort="Kawakami, Yohei" uniqKey="Kawakami Y" first="Yohei" last="Kawakami">Yohei Kawakami</name><affiliation><nlm:aff id="A1">Stem Cell Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15219</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</nlm:aff></affiliation></author><author><name sortKey="Lee, Sahnghoon" sort="Lee, Sahnghoon" uniqKey="Lee S" first="Sahnghoon" last="Lee">Sahnghoon Lee</name><affiliation><nlm:aff id="A1">Stem Cell Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15219</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</nlm:aff></affiliation></author><author><name sortKey="Greco, Nick" sort="Greco, Nick" uniqKey="Greco N" first="Nick" last="Greco">Nick Greco</name><affiliation><nlm:aff id="A1">Stem Cell Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15219</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</nlm:aff></affiliation></author><author><name sortKey="Lavasani, Mitra" sort="Lavasani, Mitra" uniqKey="Lavasani M" first="Mitra" last="Lavasani">Mitra Lavasani</name><affiliation><nlm:aff id="A1">Stem Cell Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15219</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</nlm:aff></affiliation></author><author><name sortKey="Mifune, Yutaka" sort="Mifune, Yutaka" uniqKey="Mifune Y" first="Yutaka" last="Mifune">Yutaka Mifune</name><affiliation><nlm:aff id="A1">Stem Cell Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15219</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</nlm:aff></affiliation></author><author><name sortKey="Cummins, James H" sort="Cummins, James H" uniqKey="Cummins J" first="James H." last="Cummins">James H. Cummins</name><affiliation><nlm:aff id="A1">Stem Cell Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15219</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</nlm:aff></affiliation></author><author><name sortKey="Yurube, Takashi" sort="Yurube, Takashi" uniqKey="Yurube T" first="Takashi" last="Yurube">Takashi Yurube</name><affiliation><nlm:aff id="A2">Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</nlm:aff></affiliation></author><author><name sortKey="Kuroda, Ryosuke" sort="Kuroda, Ryosuke" uniqKey="Kuroda R" first="Ryosuke" last="Kuroda">Ryosuke Kuroda</name><affiliation><nlm:aff id="A3">Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan</nlm:aff></affiliation></author><author><name sortKey="Kurosaka, Masahiro" sort="Kurosaka, Masahiro" uniqKey="Kurosaka M" first="Masahiro" last="Kurosaka">Masahiro Kurosaka</name><affiliation><nlm:aff id="A3">Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan</nlm:aff></affiliation></author><author><name sortKey="Fu, Freddie H" sort="Fu, Freddie H" uniqKey="Fu F" first="Freddie H." last="Fu">Freddie H. Fu</name><affiliation><nlm:aff id="A2">Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</nlm:aff></affiliation></author><author><name sortKey="Huard, Johnny" sort="Huard, Johnny" uniqKey="Huard J" first="Johnny" last="Huard">Johnny Huard</name><affiliation><nlm:aff id="A1">Stem Cell Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15219</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24964749</idno><idno type="pmc">4134687</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134687</idno><idno type="RBID">PMC:4134687</idno><idno type="doi">10.1002/jor.22656</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">001558</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001558</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Involvement of ERCC1 in the Pathogenesis of Osteoarthritis Through the Modulation of Apoptosis and Cellular Senescence</title><author><name sortKey="Takayama, Koji" sort="Takayama, Koji" uniqKey="Takayama K" first="Koji" last="Takayama">Koji Takayama</name><affiliation><nlm:aff id="A1">Stem Cell Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15219</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</nlm:aff></affiliation></author><author><name sortKey="Kawakami, Yohei" sort="Kawakami, Yohei" uniqKey="Kawakami Y" first="Yohei" last="Kawakami">Yohei Kawakami</name><affiliation><nlm:aff id="A1">Stem Cell Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15219</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</nlm:aff></affiliation></author><author><name sortKey="Lee, Sahnghoon" sort="Lee, Sahnghoon" uniqKey="Lee S" first="Sahnghoon" last="Lee">Sahnghoon Lee</name><affiliation><nlm:aff id="A1">Stem Cell Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15219</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</nlm:aff></affiliation></author><author><name sortKey="Greco, Nick" sort="Greco, Nick" uniqKey="Greco N" first="Nick" last="Greco">Nick Greco</name><affiliation><nlm:aff id="A1">Stem Cell Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15219</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</nlm:aff></affiliation></author><author><name sortKey="Lavasani, Mitra" sort="Lavasani, Mitra" uniqKey="Lavasani M" first="Mitra" last="Lavasani">Mitra Lavasani</name><affiliation><nlm:aff id="A1">Stem Cell Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15219</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</nlm:aff></affiliation></author><author><name sortKey="Mifune, Yutaka" sort="Mifune, Yutaka" uniqKey="Mifune Y" first="Yutaka" last="Mifune">Yutaka Mifune</name><affiliation><nlm:aff id="A1">Stem Cell Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15219</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</nlm:aff></affiliation></author><author><name sortKey="Cummins, James H" sort="Cummins, James H" uniqKey="Cummins J" first="James H." last="Cummins">James H. Cummins</name><affiliation><nlm:aff id="A1">Stem Cell Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15219</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</nlm:aff></affiliation></author><author><name sortKey="Yurube, Takashi" sort="Yurube, Takashi" uniqKey="Yurube T" first="Takashi" last="Yurube">Takashi Yurube</name><affiliation><nlm:aff id="A2">Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</nlm:aff></affiliation></author><author><name sortKey="Kuroda, Ryosuke" sort="Kuroda, Ryosuke" uniqKey="Kuroda R" first="Ryosuke" last="Kuroda">Ryosuke Kuroda</name><affiliation><nlm:aff id="A3">Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan</nlm:aff></affiliation></author><author><name sortKey="Kurosaka, Masahiro" sort="Kurosaka, Masahiro" uniqKey="Kurosaka M" first="Masahiro" last="Kurosaka">Masahiro Kurosaka</name><affiliation><nlm:aff id="A3">Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan</nlm:aff></affiliation></author><author><name sortKey="Fu, Freddie H" sort="Fu, Freddie H" uniqKey="Fu F" first="Freddie H." last="Fu">Freddie H. Fu</name><affiliation><nlm:aff id="A2">Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</nlm:aff></affiliation></author><author><name sortKey="Huard, Johnny" sort="Huard, Johnny" uniqKey="Huard J" first="Johnny" last="Huard">Johnny Huard</name><affiliation><nlm:aff id="A1">Stem Cell Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15219</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</nlm:aff></affiliation></author></analytic><series><title level="j">Journal of orthopaedic research : official publication of the Orthopaedic Research Society</title><idno type="ISSN">0736-0266</idno><idno type="eISSN">1554-527X</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="P1">DNA damage is a cause of age related pathologies, including osteoarthritis (OA). Excision repair cross complementation group 1 (ERCC1) is an endonuclease required for DNA damage repair. In this study we investigated the function of ERCC1 in chondrocytes and its association with the pathophysiology of OA. ERCC1 expression in normal and osteoarthritic cartilage was assessed, as were changes in ERCC1 expression in chondrocytes under catabolic stress. Inhibiting ERCC1 in chondrocytes under interleukin-1β stimulation using small interfering RNA (siRNA) was also evaluated. Finally, cellular senescence and apoptosis were examined in relation to ERCC1 function. ERCC1 expression was decreased in OA cartilage and increased within 4 h of exposure to interleukin (IL)-1β, but decreased after 12 h. The inhibition of ERCC1 by siRNA increased the expression of matrix metallopeptidase 13 and decreased collagen type II. ERCC1 inhibition also increased the number of apoptotic and senescent cells. The inhibition of ERCC1 in chondrocytes increased their expression of OA related proteins, apoptosis, cellular senescence, and hypertrophic-like changes which suggest that ERCC1 is critical for protecting human chondrocytes (HCs) from catabolic stresses and provides insights into the pathophysiology of OA and a potential target for its treatment.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">8404726</journal-id><journal-id journal-id-type="pubmed-jr-id">5097</journal-id><journal-id journal-id-type="nlm-ta">J Orthop Res</journal-id><journal-id journal-id-type="iso-abbrev">J. Orthop. Res.</journal-id><journal-title-group><journal-title>Journal of orthopaedic research : official publication of the Orthopaedic Research Society</journal-title></journal-title-group><issn pub-type="ppub">0736-0266</issn><issn pub-type="epub">1554-527X</issn></journal-meta><article-meta><article-id pub-id-type="pmid">24964749</article-id><article-id pub-id-type="pmc">4134687</article-id><article-id pub-id-type="doi">10.1002/jor.22656</article-id><article-id pub-id-type="manuscript">NIHMS610968</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Involvement of ERCC1 in the Pathogenesis of Osteoarthritis Through the Modulation of Apoptosis and Cellular Senescence</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Takayama</surname><given-names>Koji</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kawakami</surname><given-names>Yohei</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Lee</surname><given-names>Sahnghoon</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Greco</surname><given-names>Nick</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Lavasani</surname><given-names>Mitra</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Mifune</surname><given-names>Yutaka</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Cummins</surname><given-names>James H.</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Yurube</surname><given-names>Takashi</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Kuroda</surname><given-names>Ryosuke</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Kurosaka</surname><given-names>Masahiro</given-names></name><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>Fu</surname><given-names>Freddie H.</given-names></name><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Huard</surname><given-names>Johnny</given-names></name><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib></contrib-group><aff id="A1"><label>1</label>Stem Cell Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania 15219</aff><aff id="A2"><label>2</label>Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15213</aff><aff id="A3"><label>3</label>Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan</aff><author-notes><corresp id="cor1"><italic>Correspondence to</italic>: Johnny Huard (T: +1-412-648-2641; F: +1-412-648-4066; <email>jhuard@pitt.edu</email>)</corresp></author-notes><pub-date pub-type="nihms-submitted"><day>4</day><month>7</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>25</day><month>6</month><year>2014</year></pub-date><pub-date pub-type="ppub"><month>10</month><year>2014</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>10</month><year>2014</year></pub-date><volume>32</volume><issue>10</issue><fpage>1326</fpage><lpage>1332</lpage><pmc-comment>elocation-id from pubmed: 10.1002/jor.22656</pmc-comment>
<permissions><copyright-statement>© 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.</copyright-statement><copyright-year>2014</copyright-year></permissions><abstract><p id="P1">DNA damage is a cause of age related pathologies, including osteoarthritis (OA). Excision repair cross complementation group 1 (ERCC1) is an endonuclease required for DNA damage repair. In this study we investigated the function of ERCC1 in chondrocytes and its association with the pathophysiology of OA. ERCC1 expression in normal and osteoarthritic cartilage was assessed, as were changes in ERCC1 expression in chondrocytes under catabolic stress. Inhibiting ERCC1 in chondrocytes under interleukin-1β stimulation using small interfering RNA (siRNA) was also evaluated. Finally, cellular senescence and apoptosis were examined in relation to ERCC1 function. ERCC1 expression was decreased in OA cartilage and increased within 4 h of exposure to interleukin (IL)-1β, but decreased after 12 h. The inhibition of ERCC1 by siRNA increased the expression of matrix metallopeptidase 13 and decreased collagen type II. ERCC1 inhibition also increased the number of apoptotic and senescent cells. The inhibition of ERCC1 in chondrocytes increased their expression of OA related proteins, apoptosis, cellular senescence, and hypertrophic-like changes which suggest that ERCC1 is critical for protecting human chondrocytes (HCs) from catabolic stresses and provides insights into the pathophysiology of OA and a potential target for its treatment.</p></abstract><kwd-group><kwd>ERCC1</kwd><kwd>osteoarthritis</kwd><kwd>apoptosis</kwd><kwd>senescence</kwd><kwd>interleukin (IL)-1β</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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