Lymphatic Contribution to the Cellular Niche in Heterotopic Ossification
Identifieur interne : 003348 ( Pmc/Corpus ); précédent : 003347; suivant : 003349Lymphatic Contribution to the Cellular Niche in Heterotopic Ossification
Auteurs : Shawn Loder ; Shailesh Agarwal ; Michael Sorkin ; Chris Breuler ; John Li ; Joshua Peterson ; Hsiao Hsin Sung Hsieh ; Stewart Wang ; Babak Mehrara ; Benjamin LeviSource :
- Annals of surgery [ 0003-4932 ] ; 2016.
Abstract
The objective of this study was to determine the contribution of lymphatic tissue to heterotopic ossification.
Heterotopic ossification (HO) is the pathologic development of ectopic bone within soft tissues often following severe trauma. Characterization of the tissue niche supporting HO is critical to identifying therapies directed against this condition. Lymphangiogenesis is up-regulated during incidents of trauma, thereby co-incident with the niche supportive of HO. We hypothesized that lymphatic tissues play a critical role in HO formation.
Mice underwent hindlimb Achilles’ tendon transection and dorsal burn injury(burn/tenotomy) to induce HO. The popliteal and inguinal lymph nodes were excised ipsilateral to the tenotomy site. Flow cytometry and immunostaining were used to quantify and localize lymphoendothelium. MicroCT was used to quantify HO.
Enrichment of mature lymphatic tissues was noted 2 weeks after injury at the tendon transection sites when compared with the contralateral, intact tendon based on LYVE1+ tubules (10.9% v. 0.8%, p<0.05). Excision of the inguinal and popliteal nodes with draining popliteal lymphatic vessel significantly decreased the presence of mature lymphoendothelium 2 weeks after injury (10.9% v. 3.3%, p<0.05). Bone-cartilage-stromal progenitor cells (CD105+/AlphaV+/Tie2−/CD45−/CD90−/BP1−) were also significantly decreased after lymph node excision (10.2% v. 0.5%, p<0.05). A significant decrease was noted in the volume of
These findings suggest that lymphatic vessels are intimately linked with the formation
Url:
DOI: 10.1097/SLA.0000000000001619
PubMed: 26779981
PubMed Central: 4947025
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Lymphatic Contribution to the Cellular Niche in Heterotopic Ossification</title><author><name sortKey="Loder, Shawn" sort="Loder, Shawn" uniqKey="Loder S" first="Shawn" last="Loder">Shawn Loder</name><affiliation><nlm:aff id="A1">University of Michigan Medical School; Department of Surgery; Ann Arbor, MI USA</nlm:aff></affiliation></author><author><name sortKey="Agarwal, Shailesh" sort="Agarwal, Shailesh" uniqKey="Agarwal S" first="Shailesh" last="Agarwal">Shailesh Agarwal</name><affiliation><nlm:aff id="A1">University of Michigan Medical School; Department of Surgery; Ann Arbor, MI USA</nlm:aff></affiliation></author><author><name sortKey="Sorkin, Michael" sort="Sorkin, Michael" uniqKey="Sorkin M" first="Michael" last="Sorkin">Michael Sorkin</name><affiliation><nlm:aff id="A1">University of Michigan Medical School; Department of Surgery; Ann Arbor, MI USA</nlm:aff></affiliation></author><author><name sortKey="Breuler, Chris" sort="Breuler, Chris" uniqKey="Breuler C" first="Chris" last="Breuler">Chris Breuler</name><affiliation><nlm:aff id="A1">University of Michigan Medical School; Department of Surgery; Ann Arbor, MI USA</nlm:aff></affiliation></author><author><name sortKey="Li, John" sort="Li, John" uniqKey="Li J" first="John" last="Li">John Li</name><affiliation><nlm:aff id="A1">University of Michigan Medical School; Department of Surgery; Ann Arbor, MI USA</nlm:aff></affiliation></author><author><name sortKey="Peterson, Joshua" sort="Peterson, Joshua" uniqKey="Peterson J" first="Joshua" last="Peterson">Joshua Peterson</name><affiliation><nlm:aff id="A1">University of Michigan Medical School; Department of Surgery; Ann Arbor, MI USA</nlm:aff></affiliation></author><author><name sortKey="Hsieh, Hsiao Hsin Sung" sort="Hsieh, Hsiao Hsin Sung" uniqKey="Hsieh H" first="Hsiao Hsin Sung" last="Hsieh">Hsiao Hsin Sung Hsieh</name><affiliation><nlm:aff id="A2">Memorial Sloan Kettering; Department of Surgery, New York, NY USA</nlm:aff></affiliation></author><author><name sortKey="Wang, Stewart" sort="Wang, Stewart" uniqKey="Wang S" first="Stewart" last="Wang">Stewart Wang</name><affiliation><nlm:aff id="A1">University of Michigan Medical School; Department of Surgery; Ann Arbor, MI USA</nlm:aff></affiliation></author><author><name sortKey="Mehrara, Babak" sort="Mehrara, Babak" uniqKey="Mehrara B" first="Babak" last="Mehrara">Babak Mehrara</name><affiliation><nlm:aff id="A2">Memorial Sloan Kettering; Department of Surgery, New York, NY USA</nlm:aff></affiliation></author><author><name sortKey="Levi, Benjamin" sort="Levi, Benjamin" uniqKey="Levi B" first="Benjamin" last="Levi">Benjamin Levi</name><affiliation><nlm:aff id="A1">University of Michigan Medical School; Department of Surgery; Ann Arbor, MI USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26779981</idno><idno type="pmc">4947025</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947025</idno><idno type="RBID">PMC:4947025</idno><idno type="doi">10.1097/SLA.0000000000001619</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">003348</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">003348</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Lymphatic Contribution to the Cellular Niche in Heterotopic Ossification</title><author><name sortKey="Loder, Shawn" sort="Loder, Shawn" uniqKey="Loder S" first="Shawn" last="Loder">Shawn Loder</name><affiliation><nlm:aff id="A1">University of Michigan Medical School; Department of Surgery; Ann Arbor, MI USA</nlm:aff></affiliation></author><author><name sortKey="Agarwal, Shailesh" sort="Agarwal, Shailesh" uniqKey="Agarwal S" first="Shailesh" last="Agarwal">Shailesh Agarwal</name><affiliation><nlm:aff id="A1">University of Michigan Medical School; Department of Surgery; Ann Arbor, MI USA</nlm:aff></affiliation></author><author><name sortKey="Sorkin, Michael" sort="Sorkin, Michael" uniqKey="Sorkin M" first="Michael" last="Sorkin">Michael Sorkin</name><affiliation><nlm:aff id="A1">University of Michigan Medical School; Department of Surgery; Ann Arbor, MI USA</nlm:aff></affiliation></author><author><name sortKey="Breuler, Chris" sort="Breuler, Chris" uniqKey="Breuler C" first="Chris" last="Breuler">Chris Breuler</name><affiliation><nlm:aff id="A1">University of Michigan Medical School; Department of Surgery; Ann Arbor, MI USA</nlm:aff></affiliation></author><author><name sortKey="Li, John" sort="Li, John" uniqKey="Li J" first="John" last="Li">John Li</name><affiliation><nlm:aff id="A1">University of Michigan Medical School; Department of Surgery; Ann Arbor, MI USA</nlm:aff></affiliation></author><author><name sortKey="Peterson, Joshua" sort="Peterson, Joshua" uniqKey="Peterson J" first="Joshua" last="Peterson">Joshua Peterson</name><affiliation><nlm:aff id="A1">University of Michigan Medical School; Department of Surgery; Ann Arbor, MI USA</nlm:aff></affiliation></author><author><name sortKey="Hsieh, Hsiao Hsin Sung" sort="Hsieh, Hsiao Hsin Sung" uniqKey="Hsieh H" first="Hsiao Hsin Sung" last="Hsieh">Hsiao Hsin Sung Hsieh</name><affiliation><nlm:aff id="A2">Memorial Sloan Kettering; Department of Surgery, New York, NY USA</nlm:aff></affiliation></author><author><name sortKey="Wang, Stewart" sort="Wang, Stewart" uniqKey="Wang S" first="Stewart" last="Wang">Stewart Wang</name><affiliation><nlm:aff id="A1">University of Michigan Medical School; Department of Surgery; Ann Arbor, MI USA</nlm:aff></affiliation></author><author><name sortKey="Mehrara, Babak" sort="Mehrara, Babak" uniqKey="Mehrara B" first="Babak" last="Mehrara">Babak Mehrara</name><affiliation><nlm:aff id="A2">Memorial Sloan Kettering; Department of Surgery, New York, NY USA</nlm:aff></affiliation></author><author><name sortKey="Levi, Benjamin" sort="Levi, Benjamin" uniqKey="Levi B" first="Benjamin" last="Levi">Benjamin Levi</name><affiliation><nlm:aff id="A1">University of Michigan Medical School; Department of Surgery; Ann Arbor, MI USA</nlm:aff></affiliation></author></analytic><series><title level="j">Annals of surgery</title><idno type="ISSN">0003-4932</idno><idno type="eISSN">1528-1140</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Objective</title><p id="P1">The objective of this study was to determine the contribution of lymphatic tissue to heterotopic ossification.</p></sec><sec id="S2"><title>Background</title><p id="P2">Heterotopic ossification (HO) is the pathologic development of ectopic bone within soft tissues often following severe trauma. Characterization of the tissue niche supporting HO is critical to identifying therapies directed against this condition. Lymphangiogenesis is up-regulated during incidents of trauma, thereby co-incident with the niche supportive of HO. We hypothesized that lymphatic tissues play a critical role in HO formation.</p></sec><sec id="S3"><title>Methods</title><p id="P3">Mice underwent hindlimb Achilles’ tendon transection and dorsal burn injury(burn/tenotomy) to induce HO. The popliteal and inguinal lymph nodes were excised ipsilateral to the tenotomy site. Flow cytometry and immunostaining were used to quantify and localize lymphoendothelium. MicroCT was used to quantify HO.</p></sec><sec id="S4"><title>Results</title><p id="P4">Enrichment of mature lymphatic tissues was noted 2 weeks after injury at the tendon transection sites when compared with the contralateral, intact tendon based on LYVE1+ tubules (10.9% v. 0.8%, p<0.05). Excision of the inguinal and popliteal nodes with draining popliteal lymphatic vessel significantly decreased the presence of mature lymphoendothelium 2 weeks after injury (10.9% v. 3.3%, p<0.05). Bone-cartilage-stromal progenitor cells (CD105+/AlphaV+/Tie2−/CD45−/CD90−/BP1−) were also significantly decreased after lymph node excision (10.2% v. 0.5%, p<0.05). A significant decrease was noted in the volume of <italic>de novo</italic> HO present within the soft tissues (0.12 mm^3 v. 0.02 mm^3).</p></sec><sec id="S5"><title>Conclusions</title><p id="P5">These findings suggest that lymphatic vessels are intimately linked with the formation <italic>de novo</italic> bone within soft tissues following trauma, and their presence may facilitate bone formation.</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">0372354</journal-id><journal-id journal-id-type="pubmed-jr-id">646</journal-id><journal-id journal-id-type="nlm-ta">Ann Surg</journal-id><journal-id journal-id-type="iso-abbrev">Ann. Surg.</journal-id><journal-title-group><journal-title>Annals of surgery</journal-title></journal-title-group><issn pub-type="ppub">0003-4932</issn><issn pub-type="epub">1528-1140</issn></journal-meta><article-meta><article-id pub-id-type="pmid">26779981</article-id><article-id pub-id-type="pmc">4947025</article-id><article-id pub-id-type="doi">10.1097/SLA.0000000000001619</article-id><article-id pub-id-type="manuscript">NIHMS756424</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Lymphatic Contribution to the Cellular Niche in Heterotopic Ossification</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Loder</surname><given-names>Shawn</given-names></name><degrees>BS</degrees><xref ref-type="aff" rid="A1">1</xref><xref rid="FN2" ref-type="author-notes">*</xref></contrib><contrib contrib-type="author"><name><surname>Agarwal</surname><given-names>Shailesh</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">1</xref><xref rid="FN2" ref-type="author-notes">*</xref></contrib><contrib contrib-type="author"><name><surname>Sorkin</surname><given-names>Michael</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Breuler</surname><given-names>Chris</given-names></name><degrees>BS</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Li</surname><given-names>John</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Peterson</surname><given-names>Joshua</given-names></name><degrees>BS</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Hsieh</surname><given-names>Hsiao Hsin Sung</given-names></name><degrees>DDS</degrees><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Stewart</given-names></name><degrees>MD, PhD</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Mehrara</surname><given-names>Babak</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Levi</surname><given-names>Benjamin</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">1</xref></contrib></contrib-group><aff id="A1"><label>1</label>University of Michigan Medical School; Department of Surgery; Ann Arbor, MI USA</aff><aff id="A2"><label>2</label>Memorial Sloan Kettering; Department of Surgery, New York, NY USA</aff><author-notes><corresp id="FN1">Corresponding Authors: Benjamin Levi, MD, Assistant Professor in Surgery, University of Michigan Medical School, Department of Surgery, Division of Burn and Plastic and Reconstructive Surgery, Director, Burn Wound and Regenerative Medicine Laboratory, <email>blevi@umich.edu</email></corresp><fn id="FN2" fn-type="equal"><label>*</label><p>Indicates equal authorship.</p></fn></author-notes><pub-date pub-type="nihms-submitted"><day>4</day><month>2</month><year>2016</year></pub-date><pub-date pub-type="ppub"><month>12</month><year>2016</year></pub-date><pub-date pub-type="pmc-release"><day>01</day><month>1</month><year>2017</year></pub-date><volume>264</volume><issue>6</issue><fpage>1174</fpage><lpage>1180</lpage><pmc-comment>elocation-id from pubmed: 10.1097/SLA.0000000000001619</pmc-comment>
<abstract><sec id="S1"><title>Objective</title><p id="P1">The objective of this study was to determine the contribution of lymphatic tissue to heterotopic ossification.</p></sec><sec id="S2"><title>Background</title><p id="P2">Heterotopic ossification (HO) is the pathologic development of ectopic bone within soft tissues often following severe trauma. Characterization of the tissue niche supporting HO is critical to identifying therapies directed against this condition. Lymphangiogenesis is up-regulated during incidents of trauma, thereby co-incident with the niche supportive of HO. We hypothesized that lymphatic tissues play a critical role in HO formation.</p></sec><sec id="S3"><title>Methods</title><p id="P3">Mice underwent hindlimb Achilles’ tendon transection and dorsal burn injury(burn/tenotomy) to induce HO. The popliteal and inguinal lymph nodes were excised ipsilateral to the tenotomy site. Flow cytometry and immunostaining were used to quantify and localize lymphoendothelium. MicroCT was used to quantify HO.</p></sec><sec id="S4"><title>Results</title><p id="P4">Enrichment of mature lymphatic tissues was noted 2 weeks after injury at the tendon transection sites when compared with the contralateral, intact tendon based on LYVE1+ tubules (10.9% v. 0.8%, p<0.05). Excision of the inguinal and popliteal nodes with draining popliteal lymphatic vessel significantly decreased the presence of mature lymphoendothelium 2 weeks after injury (10.9% v. 3.3%, p<0.05). Bone-cartilage-stromal progenitor cells (CD105+/AlphaV+/Tie2−/CD45−/CD90−/BP1−) were also significantly decreased after lymph node excision (10.2% v. 0.5%, p<0.05). A significant decrease was noted in the volume of <italic>de novo</italic> HO present within the soft tissues (0.12 mm^3 v. 0.02 mm^3).</p></sec><sec id="S5"><title>Conclusions</title><p id="P5">These findings suggest that lymphatic vessels are intimately linked with the formation <italic>de novo</italic> bone within soft tissues following trauma, and their presence may facilitate bone formation.</p></sec></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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