LymphedemaV1, Pmc, Corpus, bibRecord, 003336

VEGF-C attenuates joint damage in chronic inflammatory arthritis by accelerating local lymphatic drainage

Identifieur interne : 003336 ( Pmc/Corpus ); précédent : 003335; suivant : 003337

VEGF-C attenuates joint damage in chronic inflammatory arthritis by accelerating local lymphatic drainage

Auteurs : Quan Zhou ; Ruolin Guo ; Ronald Wood ; Brendan F. Boyce ; Qianqian Liang ; Yong-Jun Wang ; Edward M. Schwarz ; Lianping Xing

Source :

Arthritis and Rheumatism [ 0004-3591 ] ; 2011.

RBID : PMC:3149728

Abstract

Objective

To investigate if enhancement of joint lymphangiogenesis by injecting VEGF-C adeno-associated virus (AAV) into joints has therapeutic efficacy in chronic inflammatory arthritis in mice.

Methods

TNF transgenic (TNF-Tg) mice were used as a model of chronic inflammatory arthritis. Human VEGF-C was cloned into an AAV expression vector to generate AAV-VEGF-C. AAV-VEGF-C or control AAV-Luc was injected into joints of TNF-Tg mice. MRI and lymphatic imaging were used during the 4-months following injection to assess changes in synovial volume and lymph flow from joint tissues to local draining lymph nodes. Joint inflammation, bone erosion and cartilage loss were examined by histologic analyses. Lymphatic vessel formation was assessed using immunohistochemistry.

Results

Intra-articular administration of AAV-VEGF-C virus significantly attenuated the increase in synovial volume and increased lymphatic vessel number in joint sections compared to AAV-Luc virus during the 4-month-period. This accompanied by reduced inflammation area, bone erosion, cartilage loss, and osteoclast numbers. Lymph flow from joints to local draining lymph nodes was slower in TNF-Tg mice than in wild-type littermates and was significantly improved with AAV-VEGF-C treatment.

Conclusion

Intra-articular injection of AAV-VEGF-C increased lymphangiogenesis and improved lymphatic drainage from inflamed joints, resulting in attenuation of joint tissue damage. Thus, improvement of joint lymphatic function by local administration of lymphatic growth factors represents a new therapeutic approach for chronic inflammatory arthritis.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149728

DOI: 10.1002/art.30421
PubMed: 21538325
PubMed Central: 3149728

Links to Exploration step

PMC:3149728

Le document en format XML

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<author><name sortKey="Zhou, Quan" sort="Zhou, Quan" uniqKey="Zhou Q" first="Quan" last="Zhou">Quan Zhou</name>
<affiliation><nlm:aff id="A1">Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Guo, Ruolin" sort="Guo, Ruolin" uniqKey="Guo R" first="Ruolin" last="Guo">Ruolin Guo</name>
<affiliation><nlm:aff id="A2">Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wood, Ronald" sort="Wood, Ronald" uniqKey="Wood R" first="Ronald" last="Wood">Ronald Wood</name>
<affiliation><nlm:aff id="A3">Department of Urology, University of Rochester Medical Center, Rochester, NY 14642, USA</nlm:aff>
</affiliation>
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<author><name sortKey="Boyce, Brendan F" sort="Boyce, Brendan F" uniqKey="Boyce B" first="Brendan F." last="Boyce">Brendan F. Boyce</name>
<affiliation><nlm:aff id="A2">Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A4">Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Liang, Qianqian" sort="Liang, Qianqian" uniqKey="Liang Q" first="Qianqian" last="Liang">Qianqian Liang</name>
<affiliation><nlm:aff id="A1">Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China</nlm:aff>
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<affiliation><nlm:aff id="A2">Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA</nlm:aff>
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<author><name sortKey="Wang, Yong Jun" sort="Wang, Yong Jun" uniqKey="Wang Y" first="Yong-Jun" last="Wang">Yong-Jun Wang</name>
<affiliation><nlm:aff id="A1">Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China</nlm:aff>
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<author><name sortKey="Schwarz, Edward M" sort="Schwarz, Edward M" uniqKey="Schwarz E" first="Edward M." last="Schwarz">Edward M. Schwarz</name>
<affiliation><nlm:aff id="A4">Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA</nlm:aff>
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<author><name sortKey="Xing, Lianping" sort="Xing, Lianping" uniqKey="Xing L" first="Lianping" last="Xing">Lianping Xing</name>
<affiliation><nlm:aff id="A2">Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA</nlm:aff>
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<affiliation><nlm:aff id="A4">Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA</nlm:aff>
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<author><name sortKey="Zhou, Quan" sort="Zhou, Quan" uniqKey="Zhou Q" first="Quan" last="Zhou">Quan Zhou</name>
<affiliation><nlm:aff id="A1">Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA</nlm:aff>
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<author><name sortKey="Guo, Ruolin" sort="Guo, Ruolin" uniqKey="Guo R" first="Ruolin" last="Guo">Ruolin Guo</name>
<affiliation><nlm:aff id="A2">Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wood, Ronald" sort="Wood, Ronald" uniqKey="Wood R" first="Ronald" last="Wood">Ronald Wood</name>
<affiliation><nlm:aff id="A3">Department of Urology, University of Rochester Medical Center, Rochester, NY 14642, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Boyce, Brendan F" sort="Boyce, Brendan F" uniqKey="Boyce B" first="Brendan F." last="Boyce">Brendan F. Boyce</name>
<affiliation><nlm:aff id="A2">Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A4">Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Liang, Qianqian" sort="Liang, Qianqian" uniqKey="Liang Q" first="Qianqian" last="Liang">Qianqian Liang</name>
<affiliation><nlm:aff id="A1">Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Wang, Yong Jun" sort="Wang, Yong Jun" uniqKey="Wang Y" first="Yong-Jun" last="Wang">Yong-Jun Wang</name>
<affiliation><nlm:aff id="A1">Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Schwarz, Edward M" sort="Schwarz, Edward M" uniqKey="Schwarz E" first="Edward M." last="Schwarz">Edward M. Schwarz</name>
<affiliation><nlm:aff id="A4">Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA</nlm:aff>
</affiliation>
</author>
<author><name sortKey="Xing, Lianping" sort="Xing, Lianping" uniqKey="Xing L" first="Lianping" last="Xing">Lianping Xing</name>
<affiliation><nlm:aff id="A2">Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A4">Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA</nlm:aff>
</affiliation>
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<series><title level="j">Arthritis and Rheumatism</title>
<idno type="ISSN">0004-3591</idno>
<idno type="eISSN">1529-0131</idno>
<imprint><date when="2011">2011</date>
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<front><div type="abstract" xml:lang="en"><sec id="S1"><title>Objective</title>
<p id="P1">To investigate if enhancement of joint lymphangiogenesis by injecting VEGF-C adeno-associated virus (AAV) into joints has therapeutic efficacy in chronic inflammatory arthritis in mice.</p>
</sec>
<sec id="S2"><title>Methods</title>
<p id="P2">TNF transgenic (TNF-Tg) mice were used as a model of chronic inflammatory arthritis. Human VEGF-C was cloned into an AAV expression vector to generate AAV-VEGF-C. AAV-VEGF-C or control AAV-Luc was injected into joints of TNF-Tg mice. MRI and lymphatic imaging were used during the 4-months following injection to assess changes in synovial volume and lymph flow from joint tissues to local draining lymph nodes. Joint inflammation, bone erosion and cartilage loss were examined by histologic analyses. Lymphatic vessel formation was assessed using immunohistochemistry.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">Intra-articular administration of AAV-VEGF-C virus significantly attenuated the increase in synovial volume and increased lymphatic vessel number in joint sections compared to AAV-Luc virus during the 4-month-period. This accompanied by reduced inflammation area, bone erosion, cartilage loss, and osteoclast numbers. Lymph flow from joints to local draining lymph nodes was slower in TNF-Tg mice than in wild-type littermates and was significantly improved with AAV-VEGF-C treatment.</p>
</sec>
<sec id="S4"><title>Conclusion</title>
<p id="P4">Intra-articular injection of AAV-VEGF-C increased lymphangiogenesis and improved lymphatic drainage from inflamed joints, resulting in attenuation of joint tissue damage. Thus, improvement of joint lymphatic function by local administration of lymphatic growth factors represents a new therapeutic approach for chronic inflammatory arthritis.</p>
</sec>
</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">0370605</journal-id>
<journal-id journal-id-type="pubmed-jr-id">881</journal-id>
<journal-id journal-id-type="nlm-ta">Arthritis Rheum</journal-id>
<journal-id journal-id-type="iso-abbrev">Arthritis Rheum.</journal-id>
<journal-title-group><journal-title>Arthritis and Rheumatism</journal-title>
</journal-title-group>
<issn pub-type="ppub">0004-3591</issn>
<issn pub-type="epub">1529-0131</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">21538325</article-id>
<article-id pub-id-type="pmc">3149728</article-id>
<article-id pub-id-type="doi">10.1002/art.30421</article-id>
<article-id pub-id-type="manuscript">NIHMS288404</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>VEGF-C attenuates joint damage in chronic inflammatory arthritis by accelerating local lymphatic drainage</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Zhou</surname>
<given-names>Quan</given-names>
</name>
<degrees>M.D., Ph.D.</degrees>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Guo</surname>
<given-names>Ruolin</given-names>
</name>
<degrees>Ph.D.</degrees>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wood</surname>
<given-names>Ronald</given-names>
</name>
<degrees>Ph.D.</degrees>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Boyce</surname>
<given-names>Brendan F.</given-names>
</name>
<degrees>M.D.</degrees>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Liang</surname>
<given-names>Qianqian</given-names>
</name>
<degrees>Ph.D.</degrees>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wang</surname>
<given-names>Yong-Jun</given-names>
</name>
<degrees>M.D., Ph.D.</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Schwarz</surname>
<given-names>Edward M.</given-names>
</name>
<degrees>Ph.D.</degrees>
<xref ref-type="aff" rid="A4">4</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Xing</surname>
<given-names>Lianping</given-names>
</name>
<degrees>Ph.D.</degrees>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A4">4</xref>
<xref ref-type="corresp" rid="cor1">5</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China</aff>
<aff id="A2"><label>2</label>
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA</aff>
<aff id="A3"><label>3</label>
Department of Urology, University of Rochester Medical Center, Rochester, NY 14642, USA</aff>
<aff id="A4"><label>4</label>
Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY 14642, USA</aff>
<author-notes><corresp id="cor1"><label>5</label>
Address correspondence to: Lianping Xing, Department of Pathology and Laboratory Medicine, 601 Elmwood Ave, Box 626, Rochester, NY 14642, Tel: 585-273-4090; Fax: 585-756-4468; <email>Lianping_xing@urmc.rochester.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>25</day>
<month>4</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="ppub"><month>8</month>
<year>2011</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>01</day>
<month>8</month>
<year>2012</year>
</pub-date>
<volume>63</volume>
<issue>8</issue>
<fpage>2318</fpage>
<lpage>2328</lpage>
<abstract><sec id="S1"><title>Objective</title>
<p id="P1">To investigate if enhancement of joint lymphangiogenesis by injecting VEGF-C adeno-associated virus (AAV) into joints has therapeutic efficacy in chronic inflammatory arthritis in mice.</p>
</sec>
<sec id="S2"><title>Methods</title>
<p id="P2">TNF transgenic (TNF-Tg) mice were used as a model of chronic inflammatory arthritis. Human VEGF-C was cloned into an AAV expression vector to generate AAV-VEGF-C. AAV-VEGF-C or control AAV-Luc was injected into joints of TNF-Tg mice. MRI and lymphatic imaging were used during the 4-months following injection to assess changes in synovial volume and lymph flow from joint tissues to local draining lymph nodes. Joint inflammation, bone erosion and cartilage loss were examined by histologic analyses. Lymphatic vessel formation was assessed using immunohistochemistry.</p>
</sec>
<sec id="S3"><title>Results</title>
<p id="P3">Intra-articular administration of AAV-VEGF-C virus significantly attenuated the increase in synovial volume and increased lymphatic vessel number in joint sections compared to AAV-Luc virus during the 4-month-period. This accompanied by reduced inflammation area, bone erosion, cartilage loss, and osteoclast numbers. Lymph flow from joints to local draining lymph nodes was slower in TNF-Tg mice than in wild-type littermates and was significantly improved with AAV-VEGF-C treatment.</p>
</sec>
<sec id="S4"><title>Conclusion</title>
<p id="P4">Intra-articular injection of AAV-VEGF-C increased lymphangiogenesis and improved lymphatic drainage from inflamed joints, resulting in attenuation of joint tissue damage. Thus, improvement of joint lymphatic function by local administration of lymphatic growth factors represents a new therapeutic approach for chronic inflammatory arthritis.</p>
</sec>
</abstract>
<kwd-group><kwd>VEGF-C</kwd>
<kwd>lymphatic system</kwd>
<kwd>lymphangiogenesis</kwd>
<kwd>inflammation</kwd>
<kwd>arthritis</kwd>
</kwd-group>
<funding-group><award-group><funding-source country="United States">National Institute of Arthritis and Musculoskeletal and Skin Diseases : NIAMS</funding-source>
<award-id>R01 AR048697-01 || AR</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
</pmc>
</record>

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VEGF-C attenuates joint damage in chronic inflammatory arthritis by accelerating local lymphatic drainage

VEGF-C attenuates joint damage in chronic inflammatory arthritis by accelerating local lymphatic drainage

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Abstract

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