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Collagen expression and biomechanical response to human recombinant transforming growth factor beta (rhTGF-β2) in the healing rabbit MCL
We investigated biomechanical and collagen expression in a healing bilateral rabbit medial collateral ligament (MCL) model to human recombinant transforming growth factor beta (rhTGF-β2) at three and six weeks. Each rabbit had rhTGF-β2 in a bioabsorbable pellet administered in one side, with the con...
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Published in: | Journal of orthopaedic research 2002-03, Vol.20 (2), p.318-324 |
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description | We investigated biomechanical and collagen expression in a healing bilateral rabbit medial collateral ligament (MCL) model to human recombinant transforming growth factor beta (rhTGF-β2) at three and six weeks. Each rabbit had rhTGF-β2 in a bioabsorbable pellet administered in one side, with the contralateral side serving as control (no rhTGF-β2). All MCL healed with rhTGF-β2 producing a profoundly increased scar mass at three weeks which decreased in size toward control at six weeks. In-situ hybridization demonstrated collagen expression (type I and III) no different than control at three weeks, but by six weeks elevated expression of type I was seen. Biomechanical analysis at three weeks showed no effect of rhTGF-β2 on structural properties. However, at six weeks rhTGF-β2 significantly inhibited both the maximum load (
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doi_str_mv | 10.1016/S0736-0266(01)00107-3 |
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p<0.05) and energy absorbed (
p<0.05) with no change in stiffness. Despite increased type I collagen expression and profound increase in early scar mass, rhTGF-β2 did not improve the structural properties. Whether the dose or mode of delivery is responsible for decline in structural properties cannot be determined in this design. We hypothesize investigations of healing ligaments to cytokines should have biologic and biomechanical properties correlated in the same study at a minimum of two time points.</description><identifier>ISSN: 0736-0266</identifier><identifier>EISSN: 1554-527X</identifier><identifier>DOI: 10.1016/S0736-0266(01)00107-3</identifier><identifier>PMID: 11918312</identifier><language>eng</language><publisher>Hoboken: Elsevier Ltd</publisher><subject>Animals ; Collagen Type I - biosynthesis ; Collagen Type I - genetics ; Disease Models, Animal ; Elasticity - drug effects ; Hindlimb - drug effects ; Hindlimb - metabolism ; Hindlimb - physiopathology ; Humans ; In Situ Hybridization ; Knee Injuries - drug therapy ; Knee Injuries - metabolism ; Knee Injuries - physiopathology ; Male ; Medial Collateral Ligament, Knee - drug effects ; Medial Collateral Ligament, Knee - metabolism ; Medial Collateral Ligament, Knee - physiopathology ; Rabbits ; Range of Motion, Articular - drug effects ; Range of Motion, Articular - physiology ; Recombinant Proteins - therapeutic use ; RNA, Messenger - metabolism ; Transforming Growth Factor beta - therapeutic use ; Transforming Growth Factor beta2 ; Weight-Bearing ; Wound Healing - drug effects</subject><ispartof>Journal of orthopaedic research, 2002-03, Vol.20 (2), p.318-324</ispartof><rights>2002 Elsevier Science Ltd</rights><rights>Copyright © 2002 Orthopaedic Research Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5032-6450b036dedc5e03c0c44920fca19960044f7dc2869561c5e58b13298aaad2e23</citedby><cites>FETCH-LOGICAL-c5032-6450b036dedc5e03c0c44920fca19960044f7dc2869561c5e58b13298aaad2e23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0736026601001073$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3549,27924,27925,45780</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11918312$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Spindler, K.P</creatorcontrib><creatorcontrib>Dawson, J.M</creatorcontrib><creatorcontrib>Stahlman, G.C</creatorcontrib><creatorcontrib>Davidson, J.M</creatorcontrib><creatorcontrib>Nanney, L.B</creatorcontrib><title>Collagen expression and biomechanical response to human recombinant transforming growth factor beta (rhTGF-β2) in the healing rabbit MCL</title><title>Journal of orthopaedic research</title><addtitle>J. Orthop. Res</addtitle><description>We investigated biomechanical and collagen expression in a healing bilateral rabbit medial collateral ligament (MCL) model to human recombinant transforming growth factor beta (rhTGF-β2) at three and six weeks. Each rabbit had rhTGF-β2 in a bioabsorbable pellet administered in one side, with the contralateral side serving as control (no rhTGF-β2). All MCL healed with rhTGF-β2 producing a profoundly increased scar mass at three weeks which decreased in size toward control at six weeks. In-situ hybridization demonstrated collagen expression (type I and III) no different than control at three weeks, but by six weeks elevated expression of type I was seen. Biomechanical analysis at three weeks showed no effect of rhTGF-β2 on structural properties. However, at six weeks rhTGF-β2 significantly inhibited both the maximum load (
p<0.05) and energy absorbed (
p<0.05) with no change in stiffness. Despite increased type I collagen expression and profound increase in early scar mass, rhTGF-β2 did not improve the structural properties. Whether the dose or mode of delivery is responsible for decline in structural properties cannot be determined in this design. We hypothesize investigations of healing ligaments to cytokines should have biologic and biomechanical properties correlated in the same study at a minimum of two time points.</description><subject>Animals</subject><subject>Collagen Type I - biosynthesis</subject><subject>Collagen Type I - genetics</subject><subject>Disease Models, Animal</subject><subject>Elasticity - drug effects</subject><subject>Hindlimb - drug effects</subject><subject>Hindlimb - metabolism</subject><subject>Hindlimb - physiopathology</subject><subject>Humans</subject><subject>In Situ Hybridization</subject><subject>Knee Injuries - drug therapy</subject><subject>Knee Injuries - metabolism</subject><subject>Knee Injuries - physiopathology</subject><subject>Male</subject><subject>Medial Collateral Ligament, Knee - drug effects</subject><subject>Medial Collateral Ligament, Knee - metabolism</subject><subject>Medial Collateral Ligament, Knee - physiopathology</subject><subject>Rabbits</subject><subject>Range of Motion, Articular - drug effects</subject><subject>Range of Motion, Articular - physiology</subject><subject>Recombinant Proteins - therapeutic use</subject><subject>RNA, Messenger - metabolism</subject><subject>Transforming Growth Factor beta - therapeutic use</subject><subject>Transforming Growth Factor beta2</subject><subject>Weight-Bearing</subject><subject>Wound Healing - drug effects</subject><issn>0736-0266</issn><issn>1554-527X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><recordid>eNqNkc1u1DAURiMEokPhEUBeoXYRuHZiJ1nxM6IDdKDSUAQ7y3FuJqaJPdge2j4Cr8OD8ExkmlFZgmTJkn3usfx9SfKYwjMKVDz_BEUmUmBCHAE9BqBQpNmdZEY5z1POiq93k9ktcpA8COEbABSUlfeTA0orWmaUzZKfc9f3ao2W4NXGYwjGWaJsQ2rjBtSdskarnow3G2cDkuhItx2UHU-0G2pjlY0kemVD6_xg7JqsvbuMHWmVjs6TGqMiR747X5ykv3-xY2IsiR2SDlW_o72qaxPJh_nyYXKvVX3AR_v9MPl88uZ8_jZdni3ezV8tU80hY6nIOdSQiQYbzREyDTrPKwatVrSqBECet0WjWSkqLuiI8LKmGatKpVTDkGWHydPJu_Hu-xZDlIMJGscULLptkAXlAirOR5BPoPYuBI-t3HgzKH8tKchdB_KmA7kLWAKVNx3IbJx7sn9gWw_Y_J3ahz4CLyfg0vR4_X9W-f5sRSkAGxfbKdJJYULEq1uF8hdSFFnB5ZePC3kqTvnqdV7K1ci_mHgck_1h0MugDVqNjRmLjLJx5h-_-gOgLbjc</recordid><startdate>200203</startdate><enddate>200203</enddate><creator>Spindler, K.P</creator><creator>Dawson, J.M</creator><creator>Stahlman, G.C</creator><creator>Davidson, J.M</creator><creator>Nanney, L.B</creator><general>Elsevier Ltd</general><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200203</creationdate><title>Collagen expression and biomechanical response to human recombinant transforming growth factor beta (rhTGF-β2) in the healing rabbit MCL</title><author>Spindler, K.P ; Dawson, J.M ; Stahlman, G.C ; Davidson, J.M ; Nanney, L.B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5032-6450b036dedc5e03c0c44920fca19960044f7dc2869561c5e58b13298aaad2e23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Collagen Type I - biosynthesis</topic><topic>Collagen Type I - genetics</topic><topic>Disease Models, Animal</topic><topic>Elasticity - drug effects</topic><topic>Hindlimb - drug effects</topic><topic>Hindlimb - metabolism</topic><topic>Hindlimb - physiopathology</topic><topic>Humans</topic><topic>In Situ Hybridization</topic><topic>Knee Injuries - drug therapy</topic><topic>Knee Injuries - metabolism</topic><topic>Knee Injuries - physiopathology</topic><topic>Male</topic><topic>Medial Collateral Ligament, Knee - drug effects</topic><topic>Medial Collateral Ligament, Knee - metabolism</topic><topic>Medial Collateral Ligament, Knee - physiopathology</topic><topic>Rabbits</topic><topic>Range of Motion, Articular - drug effects</topic><topic>Range of Motion, Articular - physiology</topic><topic>Recombinant Proteins - therapeutic use</topic><topic>RNA, Messenger - metabolism</topic><topic>Transforming Growth Factor beta - therapeutic use</topic><topic>Transforming Growth Factor beta2</topic><topic>Weight-Bearing</topic><topic>Wound Healing - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Spindler, K.P</creatorcontrib><creatorcontrib>Dawson, J.M</creatorcontrib><creatorcontrib>Stahlman, G.C</creatorcontrib><creatorcontrib>Davidson, J.M</creatorcontrib><creatorcontrib>Nanney, L.B</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of orthopaedic research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Spindler, K.P</au><au>Dawson, J.M</au><au>Stahlman, G.C</au><au>Davidson, J.M</au><au>Nanney, L.B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Collagen expression and biomechanical response to human recombinant transforming growth factor beta (rhTGF-β2) in the healing rabbit MCL</atitle><jtitle>Journal of orthopaedic research</jtitle><addtitle>J. Orthop. Res</addtitle><date>2002-03</date><risdate>2002</risdate><volume>20</volume><issue>2</issue><spage>318</spage><epage>324</epage><pages>318-324</pages><issn>0736-0266</issn><eissn>1554-527X</eissn><abstract>We investigated biomechanical and collagen expression in a healing bilateral rabbit medial collateral ligament (MCL) model to human recombinant transforming growth factor beta (rhTGF-β2) at three and six weeks. Each rabbit had rhTGF-β2 in a bioabsorbable pellet administered in one side, with the contralateral side serving as control (no rhTGF-β2). All MCL healed with rhTGF-β2 producing a profoundly increased scar mass at three weeks which decreased in size toward control at six weeks. In-situ hybridization demonstrated collagen expression (type I and III) no different than control at three weeks, but by six weeks elevated expression of type I was seen. Biomechanical analysis at three weeks showed no effect of rhTGF-β2 on structural properties. However, at six weeks rhTGF-β2 significantly inhibited both the maximum load (
p<0.05) and energy absorbed (
p<0.05) with no change in stiffness. Despite increased type I collagen expression and profound increase in early scar mass, rhTGF-β2 did not improve the structural properties. Whether the dose or mode of delivery is responsible for decline in structural properties cannot be determined in this design. We hypothesize investigations of healing ligaments to cytokines should have biologic and biomechanical properties correlated in the same study at a minimum of two time points.</abstract><cop>Hoboken</cop><pub>Elsevier Ltd</pub><pmid>11918312</pmid><doi>10.1016/S0736-0266(01)00107-3</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Collagen Type I - biosynthesis Collagen Type I - genetics Disease Models, Animal Elasticity - drug effects Hindlimb - drug effects Hindlimb - metabolism Hindlimb - physiopathology Humans In Situ Hybridization Knee Injuries - drug therapy Knee Injuries - metabolism Knee Injuries - physiopathology Male Medial Collateral Ligament, Knee - drug effects Medial Collateral Ligament, Knee - metabolism Medial Collateral Ligament, Knee - physiopathology Rabbits Range of Motion, Articular - drug effects Range of Motion, Articular - physiology Recombinant Proteins - therapeutic use RNA, Messenger - metabolism Transforming Growth Factor beta - therapeutic use Transforming Growth Factor beta2 Weight-Bearing Wound Healing - drug effects |
title | Collagen expression and biomechanical response to human recombinant transforming growth factor beta (rhTGF-β2) in the healing rabbit MCL |
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