Sildenafil accelerates fracture healing in mice
Identifieur interne : 000328 ( Main/Exploration ); précédent : 000327; suivant : 000329Sildenafil accelerates fracture healing in mice
Auteurs : Tina Histing [Allemagne] ; Kerstin Marciniak [Allemagne] ; Claudia Scheuer [Allemagne] ; Patric Garcia [Allemagne] ; Joerg H. Holstein [Allemagne] ; Moritz Klein [Allemagne] ; Romano Matthys [Suisse] ; Tim Pohlemann [Allemagne] ; Michael D. Menger [Allemagne]Source :
- Journal of Orthopaedic Research [ 0736-0266 ] ; 2011-06.
English descriptors
- KwdEn :
- Teeft :
- Angiogenesis, Angiogenic, Angiogenic response, Biomechanical, Biomechanical analysis, Biomechanical stiffness, Black columns, Body weight, Bone formation, Bone healing, Bone miner, Brous tissue, Callus, Callus area, Callus tissue, Cartilage, Cartilaginous callus callus area, Cartilaginous tissue, Enos, Enos expression, Equivalent amounts, Femur, Fracture, Fracture healing, Fracture repair, Growth factor, Growth factors, Healing, Healthcare amersham, Histing, Histomorphometric analysis, Histomorphometrical analysis, Hypercholesterolemic apolipoprotein mice, Important role, Individual animals, Intramedullary canal, June, Nitric oxide, Orthopaedic, Orthopaedic research june, Orthopaedic research society, Osseous fracture, Osteoblast, Potent stimulator, Present study, Protein expression, Radiological, Radiological analysis, Rankl, Santa cruz biotechnology, Stiffness, Total callus area, Vegf, Western blot analysis, White columns, Whole protein extracts, Wiley periodicals.
Abstract
Sildenafil, a cyclic guanosine monophosphate (cGMP)‐dependent phospodiesterase‐5 inhibitor, has been shown to be a potent stimulator of angiogenesis through upregulation of pro‐angiogenic factors and control of cGMP concentration. Herein, we determined whether sildenafil also influences angiogenic growth factor expression and bone formation during the process of fracture healing. Bone healing was studied in a murine closed femur fracture model using radiological, biomechanical, histomorphometric, and protein biochemical analysis at 2 and 5 weeks after fracture. Thirty mice received 5 mg/kg body weight sildenafil p.o. daily. Controls (n = 30) received equivalent amounts of vehicle. After 2 weeks of fracture healing sildenafil significantly increased osseous fracture bridging, as determined radiologically and histologically. This resulted in an increased biomechanical stiffness compared to controls. A smaller callus area with a slightly reduced amount of cartilaginous tissue indicated an accelerated healing process. After 5 weeks the differences were found blunted, demonstrating successful healing in both groups. Western blot analysis showed a significantly higher expression of the pro‐angiogenic and osteogenic cysteine‐rich protein (CYR) 61, confirming the increase of bone formation. We show for the first time that sildenafil treatment accelerates fracture healing by enhancing bone formation, most probably by a CYR61‐associated pathway. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:867–873
Url:
DOI: 10.1002/jor.21324
Affiliations:
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Res.</title><idno type="ISSN">0736-0266</idno><idno type="eISSN">1554-527X</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2011-06">2011-06</date><biblScope unit="volume">29</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="867">867</biblScope><biblScope unit="page" to="873">873</biblScope></imprint><idno type="ISSN">0736-0266</idno></series><idno type="istex">E84718362978E0D37B63C4D9965BE2AA92990E0A</idno><idno type="DOI">10.1002/jor.21324</idno><idno type="ArticleID">JOR21324</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0736-0266</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>CYR61</term><term>biomechanics</term><term>bone formation</term><term>fracture healing</term><term>mice</term><term>sildenafil</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Angiogenesis</term><term>Angiogenic</term><term>Angiogenic response</term><term>Biomechanical</term><term>Biomechanical analysis</term><term>Biomechanical stiffness</term><term>Black columns</term><term>Body weight</term><term>Bone formation</term><term>Bone healing</term><term>Bone miner</term><term>Brous tissue</term><term>Callus</term><term>Callus area</term><term>Callus tissue</term><term>Cartilage</term><term>Cartilaginous callus callus area</term><term>Cartilaginous tissue</term><term>Enos</term><term>Enos expression</term><term>Equivalent amounts</term><term>Femur</term><term>Fracture</term><term>Fracture healing</term><term>Fracture repair</term><term>Growth factor</term><term>Growth factors</term><term>Healing</term><term>Healthcare amersham</term><term>Histing</term><term>Histomorphometric analysis</term><term>Histomorphometrical analysis</term><term>Hypercholesterolemic apolipoprotein mice</term><term>Important role</term><term>Individual animals</term><term>Intramedullary canal</term><term>June</term><term>Nitric oxide</term><term>Orthopaedic</term><term>Orthopaedic research june</term><term>Orthopaedic research society</term><term>Osseous fracture</term><term>Osteoblast</term><term>Potent stimulator</term><term>Present study</term><term>Protein expression</term><term>Radiological</term><term>Radiological analysis</term><term>Rankl</term><term>Santa cruz biotechnology</term><term>Stiffness</term><term>Total callus area</term><term>Vegf</term><term>Western blot analysis</term><term>White columns</term><term>Whole protein extracts</term><term>Wiley periodicals</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Sildenafil, a cyclic guanosine monophosphate (cGMP)‐dependent phospodiesterase‐5 inhibitor, has been shown to be a potent stimulator of angiogenesis through upregulation of pro‐angiogenic factors and control of cGMP concentration. Herein, we determined whether sildenafil also influences angiogenic growth factor expression and bone formation during the process of fracture healing. Bone healing was studied in a murine closed femur fracture model using radiological, biomechanical, histomorphometric, and protein biochemical analysis at 2 and 5 weeks after fracture. Thirty mice received 5 mg/kg body weight sildenafil p.o. daily. Controls (n = 30) received equivalent amounts of vehicle. After 2 weeks of fracture healing sildenafil significantly increased osseous fracture bridging, as determined radiologically and histologically. This resulted in an increased biomechanical stiffness compared to controls. A smaller callus area with a slightly reduced amount of cartilaginous tissue indicated an accelerated healing process. After 5 weeks the differences were found blunted, demonstrating successful healing in both groups. Western blot analysis showed a significantly higher expression of the pro‐angiogenic and osteogenic cysteine‐rich protein (CYR) 61, confirming the increase of bone formation. We show for the first time that sildenafil treatment accelerates fracture healing by enhancing bone formation, most probably by a CYR61‐associated pathway. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:867–873</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Suisse</li></country></list><tree><country name="Allemagne"><noRegion><name sortKey="Histing, Tina" sort="Histing, Tina" uniqKey="Histing T" first="Tina" last="Histing">Tina Histing</name></noRegion><name sortKey="Garcia, Patric" sort="Garcia, Patric" uniqKey="Garcia P" first="Patric" last="Garcia">Patric Garcia</name><name sortKey="Garcia, Patric" sort="Garcia, Patric" uniqKey="Garcia P" first="Patric" last="Garcia">Patric Garcia</name><name sortKey="Histing, Tina" sort="Histing, Tina" uniqKey="Histing T" first="Tina" last="Histing">Tina Histing</name><name sortKey="Holstein, Joerg H" sort="Holstein, Joerg H" uniqKey="Holstein J" first="Joerg H." last="Holstein">Joerg H. Holstein</name><name sortKey="Holstein, Joerg H" sort="Holstein, Joerg H" uniqKey="Holstein J" first="Joerg H." last="Holstein">Joerg H. Holstein</name><name sortKey="Klein, Moritz" sort="Klein, Moritz" uniqKey="Klein M" first="Moritz" last="Klein">Moritz Klein</name><name sortKey="Klein, Moritz" sort="Klein, Moritz" uniqKey="Klein M" first="Moritz" last="Klein">Moritz Klein</name><name sortKey="Marciniak, Kerstin" sort="Marciniak, Kerstin" uniqKey="Marciniak K" first="Kerstin" last="Marciniak">Kerstin Marciniak</name><name sortKey="Marciniak, Kerstin" sort="Marciniak, Kerstin" uniqKey="Marciniak K" first="Kerstin" last="Marciniak">Kerstin Marciniak</name><name sortKey="Menger, Michael D" sort="Menger, Michael D" uniqKey="Menger M" first="Michael D." last="Menger">Michael D. Menger</name><name sortKey="Menger, Michael D" sort="Menger, Michael D" uniqKey="Menger M" first="Michael D." last="Menger">Michael D. Menger</name><name sortKey="Pohlemann, Tim" sort="Pohlemann, Tim" uniqKey="Pohlemann T" first="Tim" last="Pohlemann">Tim Pohlemann</name><name sortKey="Pohlemann, Tim" sort="Pohlemann, Tim" uniqKey="Pohlemann T" first="Tim" last="Pohlemann">Tim Pohlemann</name><name sortKey="Scheuer, Claudia" sort="Scheuer, Claudia" uniqKey="Scheuer C" first="Claudia" last="Scheuer">Claudia Scheuer</name><name sortKey="Scheuer, Claudia" sort="Scheuer, Claudia" uniqKey="Scheuer C" first="Claudia" last="Scheuer">Claudia Scheuer</name></country><country name="Suisse"><noRegion><name sortKey="Matthys, Romano" sort="Matthys, Romano" uniqKey="Matthys R" first="Romano" last="Matthys">Romano Matthys</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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