The Cellular Biology of Flexor Tendon Adhesion Formation: An Old Problem in a New Paradigm
Intrasynovial flexor tendon injuries of the hand can frequently be complicated by tendon adhesions to the surrounding sheath, limiting finger function. We have developed a new tendon injury model in the mouse to investigate the three-dimensional cellular biology of intrasynovial flexor tendon healin...
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Veröffentlicht in: | The American journal of pathology 2009-11, Vol.175 (5), p.1938-1951 |
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creator | Wong, Jason K.F Lui, Yin H Kapacee, Zoher Kadler, Karl E Ferguson, Mark W. J McGrouther, Duncan A |
description | Intrasynovial flexor tendon injuries of the hand can frequently be complicated by tendon adhesions to the surrounding sheath, limiting finger function. We have developed a new tendon injury model in the mouse to investigate the three-dimensional cellular biology of intrasynovial flexor tendon healing and adhesion formation. We investigated the cell biology using markers for inflammation, proliferation, collagen synthesis, apoptosis, and vascularization/myofibroblasts. Quantitative immunohistochemical image analysis and three-dimensional reconstruction with cell mapping was performed on labeled serial sections. Flexor tendon adhesions were also assessed 21 days after wounding using transmission electron microscopy to examine the cell phenotypes in the wound. When the tendon has been immobilized, the mouse can form tendon adhesions in the flexor tendon sheath. The cell biology of tendon healing follows the classic wound healing response of inflammation, proliferation, synthesis, and apoptosis, but the greater activity occurs in the surrounding tissue. Cells that have multiple "fibripositors" and cells with cytoplasmic protrusions that contain multiple large and small diameter fibrils can be found in the wound during collagen synthesis. In conclusion, adhesion formation occurs due to scarring between two damaged surfaces. The mouse model for flexor tendon injury represents a new platform to study adhesion formation that is genetically tractable. |
doi_str_mv | 10.2353/ajpath.2009.090380 |
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When the tendon has been immobilized, the mouse can form tendon adhesions in the flexor tendon sheath. The cell biology of tendon healing follows the classic wound healing response of inflammation, proliferation, synthesis, and apoptosis, but the greater activity occurs in the surrounding tissue. Cells that have multiple "fibripositors" and cells with cytoplasmic protrusions that contain multiple large and small diameter fibrils can be found in the wound during collagen synthesis. In conclusion, adhesion formation occurs due to scarring between two damaged surfaces. The mouse model for flexor tendon injury represents a new platform to study adhesion formation that is genetically tractable.</description><identifier>ISSN: 0002-9440</identifier><identifier>EISSN: 1525-2191</identifier><identifier>DOI: 10.2353/ajpath.2009.090380</identifier><identifier>PMID: 19834058</identifier><identifier>CODEN: AJPAA4</identifier><language>eng</language><publisher>Bethesda, MD: ASIP</publisher><subject>Animals ; Biological and medical sciences ; Biomarkers - metabolism ; Fibroblasts - cytology ; Fibroblasts - metabolism ; Finger Injuries - pathology ; Finger Injuries - physiopathology ; Humans ; Inflammation - metabolism ; Inflammation - pathology ; Investigative techniques, diagnostic techniques (general aspects) ; Male ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Microscopy, Electron, Transmission ; Models, Animal ; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques ; Pericytes - cytology ; Pericytes - metabolism ; Regular ; Tendon Injuries - pathology ; Tendon Injuries - physiopathology ; Tendons - pathology ; Tendons - physiology ; Tissue Adhesions - pathology ; Tissue Adhesions - physiopathology ; Toe Joint - pathology ; Toe Joint - physiopathology ; Wound Healing - physiology</subject><ispartof>The American journal of pathology, 2009-11, Vol.175 (5), p.1938-1951</ispartof><rights>2009 INIST-CNRS</rights><rights>Copyright © American Society for Investigative Pathology 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774058/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774058/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22119916$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19834058$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wong, Jason K.F</creatorcontrib><creatorcontrib>Lui, Yin H</creatorcontrib><creatorcontrib>Kapacee, Zoher</creatorcontrib><creatorcontrib>Kadler, Karl E</creatorcontrib><creatorcontrib>Ferguson, Mark W. J</creatorcontrib><creatorcontrib>McGrouther, Duncan A</creatorcontrib><title>The Cellular Biology of Flexor Tendon Adhesion Formation: An Old Problem in a New Paradigm</title><title>The American journal of pathology</title><addtitle>Am J Pathol</addtitle><description>Intrasynovial flexor tendon injuries of the hand can frequently be complicated by tendon adhesions to the surrounding sheath, limiting finger function. We have developed a new tendon injury model in the mouse to investigate the three-dimensional cellular biology of intrasynovial flexor tendon healing and adhesion formation. We investigated the cell biology using markers for inflammation, proliferation, collagen synthesis, apoptosis, and vascularization/myofibroblasts. Quantitative immunohistochemical image analysis and three-dimensional reconstruction with cell mapping was performed on labeled serial sections. Flexor tendon adhesions were also assessed 21 days after wounding using transmission electron microscopy to examine the cell phenotypes in the wound. When the tendon has been immobilized, the mouse can form tendon adhesions in the flexor tendon sheath. The cell biology of tendon healing follows the classic wound healing response of inflammation, proliferation, synthesis, and apoptosis, but the greater activity occurs in the surrounding tissue. Cells that have multiple "fibripositors" and cells with cytoplasmic protrusions that contain multiple large and small diameter fibrils can be found in the wound during collagen synthesis. In conclusion, adhesion formation occurs due to scarring between two damaged surfaces. The mouse model for flexor tendon injury represents a new platform to study adhesion formation that is genetically tractable.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - metabolism</subject><subject>Fibroblasts - cytology</subject><subject>Fibroblasts - metabolism</subject><subject>Finger Injuries - pathology</subject><subject>Finger Injuries - physiopathology</subject><subject>Humans</subject><subject>Inflammation - metabolism</subject><subject>Inflammation - pathology</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microscopy, Electron, Transmission</subject><subject>Models, Animal</subject><subject>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</subject><subject>Pericytes - cytology</subject><subject>Pericytes - metabolism</subject><subject>Regular</subject><subject>Tendon Injuries - pathology</subject><subject>Tendon Injuries - physiopathology</subject><subject>Tendons - pathology</subject><subject>Tendons - physiology</subject><subject>Tissue Adhesions - pathology</subject><subject>Tissue Adhesions - physiopathology</subject><subject>Toe Joint - pathology</subject><subject>Toe Joint - physiopathology</subject><subject>Wound Healing - physiology</subject><issn>0002-9440</issn><issn>1525-2191</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1O3DAURi1UVAboC7BA3lRdZfBP7MQsKk1HTIuECovpphvrOnEmRk482JlS3r5GHaBd-Vo-Ot_VZ4TOKJkzLvgF3G9h6ueMEDUnivCaHKAZFUwUjCr6Ds0IIaxQZUmO0HFK9_kqM_QeHVFV85KIeoZ-rnuLl9b7nYeIv7jgw-YJhw6vvP0dIl7bsQ0jXrS9TS4PqxAHmPJ0iRcjvvUtvovBeDtgN2LA3-0jvoMIrdsMp-iwA5_sh_15gn6srtbLb8XN7dfr5eKm6DmrpqIzCpiSxLSMVVSWLbcGOps3pJ2VlYQaTE0FodQoVRkQHVOmKTsphQBVS36CPv_1bndmsG1jxymC19voBohPOoDT_7-Mrteb8EuzqnouIQs-7QUxPOxsmvTgUpM7gdGGXdIV56oUSrFMnv8b9Zrx0mcGPu4BSA34LsLYuPTKMUapUlS-RfZu0z-6aHUawPuspTp_K62EFtnKa_4HP5iTQg</recordid><startdate>20091101</startdate><enddate>20091101</enddate><creator>Wong, Jason K.F</creator><creator>Lui, Yin H</creator><creator>Kapacee, Zoher</creator><creator>Kadler, Karl E</creator><creator>Ferguson, Mark W. J</creator><creator>McGrouther, Duncan A</creator><general>ASIP</general><general>American Society for Investigative Pathology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20091101</creationdate><title>The Cellular Biology of Flexor Tendon Adhesion Formation: An Old Problem in a New Paradigm</title><author>Wong, Jason K.F ; Lui, Yin H ; Kapacee, Zoher ; Kadler, Karl E ; Ferguson, Mark W. J ; McGrouther, Duncan A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h327t-fb9a2960bd227164d3ebafe9831fe676a8ab815011b997ba5f29bc4f6655a9863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - metabolism</topic><topic>Fibroblasts - cytology</topic><topic>Fibroblasts - metabolism</topic><topic>Finger Injuries - pathology</topic><topic>Finger Injuries - physiopathology</topic><topic>Humans</topic><topic>Inflammation - metabolism</topic><topic>Inflammation - pathology</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microscopy, Electron, Transmission</topic><topic>Models, Animal</topic><topic>Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques</topic><topic>Pericytes - cytology</topic><topic>Pericytes - metabolism</topic><topic>Regular</topic><topic>Tendon Injuries - pathology</topic><topic>Tendon Injuries - physiopathology</topic><topic>Tendons - pathology</topic><topic>Tendons - physiology</topic><topic>Tissue Adhesions - pathology</topic><topic>Tissue Adhesions - physiopathology</topic><topic>Toe Joint - pathology</topic><topic>Toe Joint - physiopathology</topic><topic>Wound Healing - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wong, Jason K.F</creatorcontrib><creatorcontrib>Lui, Yin H</creatorcontrib><creatorcontrib>Kapacee, Zoher</creatorcontrib><creatorcontrib>Kadler, Karl E</creatorcontrib><creatorcontrib>Ferguson, Mark W. J</creatorcontrib><creatorcontrib>McGrouther, Duncan A</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The American journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wong, Jason K.F</au><au>Lui, Yin H</au><au>Kapacee, Zoher</au><au>Kadler, Karl E</au><au>Ferguson, Mark W. J</au><au>McGrouther, Duncan A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Cellular Biology of Flexor Tendon Adhesion Formation: An Old Problem in a New Paradigm</atitle><jtitle>The American journal of pathology</jtitle><addtitle>Am J Pathol</addtitle><date>2009-11-01</date><risdate>2009</risdate><volume>175</volume><issue>5</issue><spage>1938</spage><epage>1951</epage><pages>1938-1951</pages><issn>0002-9440</issn><eissn>1525-2191</eissn><coden>AJPAA4</coden><abstract>Intrasynovial flexor tendon injuries of the hand can frequently be complicated by tendon adhesions to the surrounding sheath, limiting finger function. We have developed a new tendon injury model in the mouse to investigate the three-dimensional cellular biology of intrasynovial flexor tendon healing and adhesion formation. We investigated the cell biology using markers for inflammation, proliferation, collagen synthesis, apoptosis, and vascularization/myofibroblasts. Quantitative immunohistochemical image analysis and three-dimensional reconstruction with cell mapping was performed on labeled serial sections. Flexor tendon adhesions were also assessed 21 days after wounding using transmission electron microscopy to examine the cell phenotypes in the wound. When the tendon has been immobilized, the mouse can form tendon adhesions in the flexor tendon sheath. The cell biology of tendon healing follows the classic wound healing response of inflammation, proliferation, synthesis, and apoptosis, but the greater activity occurs in the surrounding tissue. Cells that have multiple "fibripositors" and cells with cytoplasmic protrusions that contain multiple large and small diameter fibrils can be found in the wound during collagen synthesis. In conclusion, adhesion formation occurs due to scarring between two damaged surfaces. The mouse model for flexor tendon injury represents a new platform to study adhesion formation that is genetically tractable.</abstract><cop>Bethesda, MD</cop><pub>ASIP</pub><pmid>19834058</pmid><doi>10.2353/ajpath.2009.090380</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Biological and medical sciences Biomarkers - metabolism Fibroblasts - cytology Fibroblasts - metabolism Finger Injuries - pathology Finger Injuries - physiopathology Humans Inflammation - metabolism Inflammation - pathology Investigative techniques, diagnostic techniques (general aspects) Male Medical sciences Mice Mice, Inbred C57BL Microscopy, Electron, Transmission Models, Animal Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Pericytes - cytology Pericytes - metabolism Regular Tendon Injuries - pathology Tendon Injuries - physiopathology Tendons - pathology Tendons - physiology Tissue Adhesions - pathology Tissue Adhesions - physiopathology Toe Joint - pathology Toe Joint - physiopathology Wound Healing - physiology |
title | The Cellular Biology of Flexor Tendon Adhesion Formation: An Old Problem in a New Paradigm |
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