The tumour-associated glycoprotein podoplanin is expressed in fibroblast-like synoviocytes of the hyperplastic synovial lining layer in rheumatoid arthritis
Identifieur interne : 002C70 ( Pmc/Checkpoint ); précédent : 002C69; suivant : 002C71The tumour-associated glycoprotein podoplanin is expressed in fibroblast-like synoviocytes of the hyperplastic synovial lining layer in rheumatoid arthritis
Auteurs : Anna-Karin H. Ekwall [Suède] ; Thomas Eisler [Suède] ; Christian Anderberg [Suède] ; Chunsheng Jin [Suède] ; Niclas Karlsson [Suède] ; Mikael Brisslert [Suède] ; Maria I. Bokarewa [Suède]Source :
- Arthritis Research & Therapy [ 1478-6354 ] ; 2011.
Abstract
Activated fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) share many characteristics with tumour cells and are key mediators of synovial tissue transformation and joint destruction. The glycoprotein podoplanin is upregulated in the invasive front of several human cancers and has been associated with epithelial-mesenchymal transition, increased cell migration and tissue invasion. The aim of this study was to investigate whether podoplanin is expressed in areas of synovial transformation in RA and especially in promigratory RA-FLS.
Podoplanin expression in human synovial tissue from 18 RA patients and nine osteoarthritis (OA) patients was assessed by immunohistochemistry and confirmed by Western blot analysis. The expression was related to markers of synoviocytes and myofibroblasts detected by using confocal immunofluoresence microscopy. Expression of podoplanin, with or without the addition of proinflammatory cytokines and growth factors, in primary human FLS was evaluated by using flow cytometry.
Podoplanin was highly expressed in cadherin-11-positive cells throughout the synovial lining layer in RA. The expression was most pronounced in areas with lining layer hyperplasia and high matrix metalloproteinase 9 expression, where it coincided with upregulation of α-smooth muscle actin (α-sma). The synovium in OA was predominantly podoplanin-negative. Podoplanin was expressed in 50% of cultured primary FLSs, and the expression was increased by interleukin 1β, tumour necrosis factor α and transforming growth factor β receptor 1.
Here we show that podoplanin is highly expressed in FLSs of the invading synovial tissue in RA. The concomitant upregulation of α-sma and podoplanin in a subpopulation of FLSs indicates a myofibroblast phenotype. Proinflammatory mediators increased the podoplanin expression in cultured RA-FLS. We conclude that podoplanin might be involved in the synovial tissue transformation and increased migratory potential of activated FLSs in RA.
Url:
DOI: 10.1186/ar3274
PubMed: 21385358
PubMed Central: 3132020
Affiliations:
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<series><title level="j">Arthritis Research & Therapy</title>
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<front><div type="abstract" xml:lang="en"><sec><title>Introduction</title>
<p>Activated fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) share many characteristics with tumour cells and are key mediators of synovial tissue transformation and joint destruction. The glycoprotein podoplanin is upregulated in the invasive front of several human cancers and has been associated with epithelial-mesenchymal transition, increased cell migration and tissue invasion. The aim of this study was to investigate whether podoplanin is expressed in areas of synovial transformation in RA and especially in promigratory RA-FLS.</p>
</sec>
<sec><title>Methods</title>
<p>Podoplanin expression in human synovial tissue from 18 RA patients and nine osteoarthritis (OA) patients was assessed by immunohistochemistry and confirmed by Western blot analysis. The expression was related to markers of synoviocytes and myofibroblasts detected by using confocal immunofluoresence microscopy. Expression of podoplanin, with or without the addition of proinflammatory cytokines and growth factors, in primary human FLS was evaluated by using flow cytometry.</p>
</sec>
<sec><title>Results</title>
<p>Podoplanin was highly expressed in cadherin-11-positive cells throughout the synovial lining layer in RA. The expression was most pronounced in areas with lining layer hyperplasia and high matrix metalloproteinase 9 expression, where it coincided with upregulation of α-smooth muscle actin (α-sma). The synovium in OA was predominantly podoplanin-negative. Podoplanin was expressed in 50% of cultured primary FLSs, and the expression was increased by interleukin 1β, tumour necrosis factor α and transforming growth factor β receptor 1.</p>
</sec>
<sec><title>Conclusions</title>
<p>Here we show that podoplanin is highly expressed in FLSs of the invading synovial tissue in RA. The concomitant upregulation of α-sma and podoplanin in a subpopulation of FLSs indicates a myofibroblast phenotype. Proinflammatory mediators increased the podoplanin expression in cultured RA-FLS. We conclude that podoplanin might be involved in the synovial tissue transformation and increased migratory potential of activated FLSs in RA.</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">Arthritis Res Ther</journal-id>
<journal-title-group><journal-title>Arthritis Research & Therapy</journal-title>
</journal-title-group>
<issn pub-type="ppub">1478-6354</issn>
<issn pub-type="epub">1478-6362</issn>
<publisher><publisher-name>BioMed Central</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">21385358</article-id>
<article-id pub-id-type="pmc">3132020</article-id>
<article-id pub-id-type="publisher-id">ar3274</article-id>
<article-id pub-id-type="doi">10.1186/ar3274</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>The tumour-associated glycoprotein podoplanin is expressed in fibroblast-like synoviocytes of the hyperplastic synovial lining layer in rheumatoid arthritis</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" corresp="yes" id="A1"><name><surname>Ekwall</surname>
<given-names>Anna-Karin H</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>anna-karin.hultgard.ekwall@rheuma.gu.se</email>
</contrib>
<contrib contrib-type="author" id="A2"><name><surname>Eisler</surname>
<given-names>Thomas</given-names>
</name>
<xref ref-type="aff" rid="I2">2</xref>
<email>thomas.eisler@ds.se</email>
</contrib>
<contrib contrib-type="author" id="A3"><name><surname>Anderberg</surname>
<given-names>Christian</given-names>
</name>
<xref ref-type="aff" rid="I3">3</xref>
<email>christian.anderberg@spenshult.se</email>
</contrib>
<contrib contrib-type="author" id="A4"><name><surname>Jin</surname>
<given-names>Chunsheng</given-names>
</name>
<xref ref-type="aff" rid="I4">4</xref>
<email>chunsheng.jin@medkem.gu.se</email>
</contrib>
<contrib contrib-type="author" id="A5"><name><surname>Karlsson</surname>
<given-names>Niclas</given-names>
</name>
<xref ref-type="aff" rid="I4">4</xref>
<email>niclas.karlsson@medkem.gu.se</email>
</contrib>
<contrib contrib-type="author" id="A6"><name><surname>Brisslert</surname>
<given-names>Mikael</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>mikael.brisslert@rheuma.gu.se</email>
</contrib>
<contrib contrib-type="author" id="A7"><name><surname>Bokarewa</surname>
<given-names>Maria I</given-names>
</name>
<xref ref-type="aff" rid="I1">1</xref>
<email>maria.bokarewa@rheuma.gu.se</email>
</contrib>
</contrib-group>
<aff id="I1"><label>1</label>
Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, Göteborg University, Box 480, 405 30 Göteborg, Sweden</aff>
<aff id="I2"><label>2</label>
Department of Orthopaedics, Institute of Clinical Sciences, Sahlgrenska Academy, Göteborg University, Bruna Stråket 11, 314 45 Göteborg, Sweden</aff>
<aff id="I3"><label>3</label>
Division of Orthopaedics, Spenshult Hospital, 313 92 Oskarström, Sweden</aff>
<aff id="I4"><label>4</label>
Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, Sahlgrenska Academy, Göteborg University, Box 440, 405 30 Göteborg, Sweden</aff>
<pub-date pub-type="ppub"><year>2011</year>
</pub-date>
<pub-date pub-type="epub"><day>7</day>
<month>3</month>
<year>2011</year>
</pub-date>
<volume>13</volume>
<issue>2</issue>
<fpage>R40</fpage>
<lpage>R40</lpage>
<history><date date-type="received"><day>10</day>
<month>9</month>
<year>2010</year>
</date>
<date date-type="rev-recd"><day>11</day>
<month>1</month>
<year>2011</year>
</date>
<date date-type="accepted"><day>7</day>
<month>3</month>
<year>2011</year>
</date>
</history>
<permissions><copyright-statement>Copyright ©2011 Ekwall et al.; licensee BioMed Central Ltd.</copyright-statement>
<copyright-year>2011</copyright-year>
<copyright-holder>Ekwall et al.; licensee BioMed Central Ltd.</copyright-holder>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/2.0"><license-p>This is an open access article distributed under the terms of the Creative Commons Attribution License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/2.0">http://creativecommons.org/licenses/by/2.0</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<self-uri xlink:href="http://arthritis-research.com/content/13/2/R40"></self-uri>
<abstract><sec><title>Introduction</title>
<p>Activated fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) share many characteristics with tumour cells and are key mediators of synovial tissue transformation and joint destruction. The glycoprotein podoplanin is upregulated in the invasive front of several human cancers and has been associated with epithelial-mesenchymal transition, increased cell migration and tissue invasion. The aim of this study was to investigate whether podoplanin is expressed in areas of synovial transformation in RA and especially in promigratory RA-FLS.</p>
</sec>
<sec><title>Methods</title>
<p>Podoplanin expression in human synovial tissue from 18 RA patients and nine osteoarthritis (OA) patients was assessed by immunohistochemistry and confirmed by Western blot analysis. The expression was related to markers of synoviocytes and myofibroblasts detected by using confocal immunofluoresence microscopy. Expression of podoplanin, with or without the addition of proinflammatory cytokines and growth factors, in primary human FLS was evaluated by using flow cytometry.</p>
</sec>
<sec><title>Results</title>
<p>Podoplanin was highly expressed in cadherin-11-positive cells throughout the synovial lining layer in RA. The expression was most pronounced in areas with lining layer hyperplasia and high matrix metalloproteinase 9 expression, where it coincided with upregulation of α-smooth muscle actin (α-sma). The synovium in OA was predominantly podoplanin-negative. Podoplanin was expressed in 50% of cultured primary FLSs, and the expression was increased by interleukin 1β, tumour necrosis factor α and transforming growth factor β receptor 1.</p>
</sec>
<sec><title>Conclusions</title>
<p>Here we show that podoplanin is highly expressed in FLSs of the invading synovial tissue in RA. The concomitant upregulation of α-sma and podoplanin in a subpopulation of FLSs indicates a myofibroblast phenotype. Proinflammatory mediators increased the podoplanin expression in cultured RA-FLS. We conclude that podoplanin might be involved in the synovial tissue transformation and increased migratory potential of activated FLSs in RA.</p>
</sec>
</abstract>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>Suède</li>
</country>
<region><li>Götaland</li>
<li>Suède occidentale</li>
</region>
<settlement><li>Göteborg</li>
</settlement>
<orgName><li>Université de Göteborg</li>
</orgName>
</list>
<tree><country name="Suède"><region name="Götaland"><name sortKey="Ekwall, Anna Karin H" sort="Ekwall, Anna Karin H" uniqKey="Ekwall A" first="Anna-Karin H" last="Ekwall">Anna-Karin H. Ekwall</name>
</region>
<name sortKey="Anderberg, Christian" sort="Anderberg, Christian" uniqKey="Anderberg C" first="Christian" last="Anderberg">Christian Anderberg</name>
<name sortKey="Bokarewa, Maria I" sort="Bokarewa, Maria I" uniqKey="Bokarewa M" first="Maria I" last="Bokarewa">Maria I. Bokarewa</name>
<name sortKey="Brisslert, Mikael" sort="Brisslert, Mikael" uniqKey="Brisslert M" first="Mikael" last="Brisslert">Mikael Brisslert</name>
<name sortKey="Eisler, Thomas" sort="Eisler, Thomas" uniqKey="Eisler T" first="Thomas" last="Eisler">Thomas Eisler</name>
<name sortKey="Jin, Chunsheng" sort="Jin, Chunsheng" uniqKey="Jin C" first="Chunsheng" last="Jin">Chunsheng Jin</name>
<name sortKey="Karlsson, Niclas" sort="Karlsson, Niclas" uniqKey="Karlsson N" first="Niclas" last="Karlsson">Niclas Karlsson</name>
</country>
</tree>
</affiliations>
</record>
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