Peripheral denervation participates in heterotopic ossification in a spinal cord injury model
Identifieur interne : 004D62 ( Ncbi/Curation ); précédent : 004D61; suivant : 004D63Peripheral denervation participates in heterotopic ossification in a spinal cord injury model
Auteurs : Charlotte Debaud [France] ; Marjorie Salga [France] ; Laurent Begot [France] ; Xavier Holy [France] ; Malha Chedik [France] ; Nicolas De L Scalopier [France] ; Fréderic Torossian [France] ; Jean-Pierre Levesque [Australie] ; Jean-Jacques Lataillade [France] ; Marie-Caroline Le Bousse-Kerdilès [France] ; François Genêt [France]Source :
- PLoS ONE [ 1932-6203 ] ; 2017.
Descripteurs français
- KwdFr :
- Animaux, Cardiotoxines de venin de cobra, Dénervation, Femelle, Microtomographie aux rayons X, Modèles animaux de maladie humaine, Moelle spinale (), Moelle spinale (anatomopathologie), Moelle spinale (imagerie diagnostique), Muscles (), Muscles (anatomopathologie), Muscles (innervation), Ossification hétérotopique (), Ossification hétérotopique (anatomopathologie), Ossification hétérotopique (imagerie diagnostique), Ossification hétérotopique (étiologie), Protéine morphogénétique osseuse de type 2 (analyse), Souris de lignée C57BL, Traumatismes de la moelle épinière (), Traumatismes de la moelle épinière (anatomopathologie), Traumatismes de la moelle épinière (imagerie diagnostique), Traumatismes de la moelle épinière (étiologie).
- MESH :
- analyse : Protéine morphogénétique osseuse de type 2.
- anatomopathologie : Moelle spinale, Muscles, Ossification hétérotopique, Traumatismes de la moelle épinière.
- imagerie diagnostique : Moelle spinale, Ossification hétérotopique, Traumatismes de la moelle épinière.
- étiologie : Muscles, Ossification hétérotopique, Traumatismes de la moelle épinière.
- Animaux, Cardiotoxines de venin de cobra, Dénervation, Femelle, Microtomographie aux rayons X, Modèles animaux de maladie humaine, Moelle spinale, Muscles, Ossification hétérotopique, Souris de lignée C57BL, Traumatismes de la moelle épinière.
English descriptors
- KwdEn :
- Animals, Bone Morphogenetic Protein 2 (analysis), Cobra Cardiotoxin Proteins, Denervation, Disease Models, Animal, Female, Mice, Inbred C57BL, Muscles (drug effects), Muscles (innervation), Muscles (pathology), Ossification, Heterotopic (chemically induced), Ossification, Heterotopic (diagnostic imaging), Ossification, Heterotopic (etiology), Ossification, Heterotopic (pathology), Spinal Cord (diagnostic imaging), Spinal Cord (drug effects), Spinal Cord (pathology), Spinal Cord Injuries (chemically induced), Spinal Cord Injuries (diagnostic imaging), Spinal Cord Injuries (etiology), Spinal Cord Injuries (pathology), X-Ray Microtomography.
- MESH :
- chemical , analysis : Bone Morphogenetic Protein 2.
- chemically induced : Ossification, Heterotopic, Spinal Cord Injuries.
- diagnostic imaging : Ossification, Heterotopic, Spinal Cord, Spinal Cord Injuries.
- drug effects : Muscles, Spinal Cord.
- etiology : Ossification, Heterotopic, Spinal Cord Injuries.
- innervation : Muscles.
- pathology : Muscles, Ossification, Heterotopic, Spinal Cord, Spinal Cord Injuries.
- Animals, Cobra Cardiotoxin Proteins, Denervation, Disease Models, Animal, Female, Mice, Inbred C57BL, X-Ray Microtomography.
Abstract
We previously reported the development of a new acquired neurogenic HO (NHO) mouse model, combining spinal cord transection (SCI) and chemical muscle injury. Pathological mechanisms responsible for ectopic osteogenesis after central neurological damage are still to be elucidated. In this study, we first hypothesized that peripheral nervous system (PNS) might convey pathological signals from injured spinal cord to muscles in NHO mouse model. Secondly, we sought to determine whether SCI could lead to intramuscular modifications of BMP2 signaling pathways. Twenty one C57Bl6 mice were included in this protocol. Bilateral cardiotoxin (CTX) injection in hamstring muscles was associated with a two-stage surgical procedure, combining thoracic SCI with unilateral peripheral denervation. Volumes of HO (Bone Volume, BV) were measured 28 days after surgery using micro-computed tomography imaging techniques and histological analyses were made to confirm intramuscular osteogenesis. Volume comparisons were conducted between right and left hind limb of each animal, using a Wilcoxon signed rank test. Quantitative polymerase chain reaction (qPCR) was performed to explore intra muscular expression of BMP2, Alk3 and Id1. Nineteen mice survive the complete SCI and peripheral denervation procedure. When CTX injections were done right after surgery (n = 7), bilateral HO were detected in all animals after 28 days. Micro-CT measurements showed significantly increased BV in denervated paws (1.47 mm3 +/- 0.5) compared to contralateral sides (0.56 mm3 +/-0.4), p = 0.03. When peripheral denervation and CTX injections were performed after sham SCI surgery (n = 6), bilateral HO were present in three mice at day 28. Quantitative PCR analyses showed no changes in intra muscular BMP2 expression after SCI as compared to control mice (shamSCI). Peripheral denervation can be reliably added to spinal cord transection in NHO mouse model. This new experimental design confirms that neuro inflammatory mechanisms induced by central or peripheral nervous system injury plays a key role in triggering ectopic osteogenesis.
Url:
DOI: 10.1371/journal.pone.0182454
PubMed: 28854256
PubMed Central: 5576715
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PMC:5576715Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Peripheral denervation participates in heterotopic ossification in a spinal cord injury model</title>
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<author><name sortKey="Torossian, Frederic" sort="Torossian, Frederic" uniqKey="Torossian F" first="Fréderic" last="Torossian">Fréderic Torossian</name>
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<author><name sortKey="Levesque, Jean Pierre" sort="Levesque, Jean Pierre" uniqKey="Levesque J" first="Jean-Pierre" last="Levesque">Jean-Pierre Levesque</name>
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<author><name sortKey="Lataillade, Jean Jacques" sort="Lataillade, Jean Jacques" uniqKey="Lataillade J" first="Jean-Jacques" last="Lataillade">Jean-Jacques Lataillade</name>
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</nlm:aff>
<country xml:lang="fr">France</country>
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<author><name sortKey="Le Bousse Kerdiles, Marie Caroline" sort="Le Bousse Kerdiles, Marie Caroline" uniqKey="Le Bousse Kerdiles M" first="Marie-Caroline" last="Le Bousse-Kerdilès">Marie-Caroline Le Bousse-Kerdilès</name>
<affiliation wicri:level="1"><nlm:aff id="aff006"><addr-line>University of Paris-Sud, INSERM UMR-S/MD 1197, Hôpital Paul Brousse, APHP, Villejuif, France</addr-line>
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<country xml:lang="fr">France</country>
<wicri:regionArea>University of Paris-Sud, INSERM UMR-S/MD 1197, Hôpital Paul Brousse, APHP, Villejuif</wicri:regionArea>
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<wicri:noRegion>Villejuif</wicri:noRegion>
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</author>
<author><name sortKey="Genet, Francois" sort="Genet, Francois" uniqKey="Genet F" first="François" last="Genêt">François Genêt</name>
<affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>University of Versailles Saint Quentin en Yvelines, U1179 INSERM, UFR des Sciences de la Santé – Simone Veil, Montigny-le-Bretonneux, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>University of Versailles Saint Quentin en Yvelines, U1179 INSERM, UFR des Sciences de la Santé – Simone Veil, Montigny-le-Bretonneux</wicri:regionArea>
<wicri:noRegion>Montigny-le-Bretonneux</wicri:noRegion>
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<affiliation wicri:level="1"><nlm:aff id="aff003"><addr-line>Rehabilitation Service, Hôpital Raymond Poincaré, APHP, CIC-IT 1429, Garches, France</addr-line>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Rehabilitation Service, Hôpital Raymond Poincaré, APHP, CIC-IT 1429, Garches</wicri:regionArea>
<wicri:noRegion>Garches</wicri:noRegion>
<wicri:noRegion>Garches</wicri:noRegion>
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<series><title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint><date when="2017">2017</date>
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<term>Bone Morphogenetic Protein 2 (analysis)</term>
<term>Cobra Cardiotoxin Proteins</term>
<term>Denervation</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Mice, Inbred C57BL</term>
<term>Muscles (drug effects)</term>
<term>Muscles (innervation)</term>
<term>Muscles (pathology)</term>
<term>Ossification, Heterotopic (chemically induced)</term>
<term>Ossification, Heterotopic (diagnostic imaging)</term>
<term>Ossification, Heterotopic (etiology)</term>
<term>Ossification, Heterotopic (pathology)</term>
<term>Spinal Cord (diagnostic imaging)</term>
<term>Spinal Cord (drug effects)</term>
<term>Spinal Cord (pathology)</term>
<term>Spinal Cord Injuries (chemically induced)</term>
<term>Spinal Cord Injuries (diagnostic imaging)</term>
<term>Spinal Cord Injuries (etiology)</term>
<term>Spinal Cord Injuries (pathology)</term>
<term>X-Ray Microtomography</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term>
<term>Cardiotoxines de venin de cobra</term>
<term>Dénervation</term>
<term>Femelle</term>
<term>Microtomographie aux rayons X</term>
<term>Modèles animaux de maladie humaine</term>
<term>Moelle spinale ()</term>
<term>Moelle spinale (anatomopathologie)</term>
<term>Moelle spinale (imagerie diagnostique)</term>
<term>Muscles ()</term>
<term>Muscles (anatomopathologie)</term>
<term>Muscles (innervation)</term>
<term>Ossification hétérotopique ()</term>
<term>Ossification hétérotopique (anatomopathologie)</term>
<term>Ossification hétérotopique (imagerie diagnostique)</term>
<term>Ossification hétérotopique (étiologie)</term>
<term>Protéine morphogénétique osseuse de type 2 (analyse)</term>
<term>Souris de lignée C57BL</term>
<term>Traumatismes de la moelle épinière ()</term>
<term>Traumatismes de la moelle épinière (anatomopathologie)</term>
<term>Traumatismes de la moelle épinière (imagerie diagnostique)</term>
<term>Traumatismes de la moelle épinière (étiologie)</term>
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<keywords scheme="MESH" qualifier="analyse" xml:lang="fr"><term>Protéine morphogénétique osseuse de type 2</term>
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<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Moelle spinale</term>
<term>Muscles</term>
<term>Ossification hétérotopique</term>
<term>Traumatismes de la moelle épinière</term>
</keywords>
<keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Ossification, Heterotopic</term>
<term>Spinal Cord Injuries</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnostic imaging" xml:lang="en"><term>Ossification, Heterotopic</term>
<term>Spinal Cord</term>
<term>Spinal Cord Injuries</term>
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<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Muscles</term>
<term>Spinal Cord</term>
</keywords>
<keywords scheme="MESH" qualifier="etiology" xml:lang="en"><term>Ossification, Heterotopic</term>
<term>Spinal Cord Injuries</term>
</keywords>
<keywords scheme="MESH" qualifier="imagerie diagnostique" xml:lang="fr"><term>Moelle spinale</term>
<term>Ossification hétérotopique</term>
<term>Traumatismes de la moelle épinière</term>
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<keywords scheme="MESH" qualifier="innervation" xml:lang="en"><term>Muscles</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Muscles</term>
<term>Ossification, Heterotopic</term>
<term>Spinal Cord</term>
<term>Spinal Cord Injuries</term>
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<keywords scheme="MESH" qualifier="étiologie" xml:lang="fr"><term>Muscles</term>
<term>Ossification hétérotopique</term>
<term>Traumatismes de la moelle épinière</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Cobra Cardiotoxin Proteins</term>
<term>Denervation</term>
<term>Disease Models, Animal</term>
<term>Female</term>
<term>Mice, Inbred C57BL</term>
<term>X-Ray Microtomography</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Animaux</term>
<term>Cardiotoxines de venin de cobra</term>
<term>Dénervation</term>
<term>Femelle</term>
<term>Microtomographie aux rayons X</term>
<term>Modèles animaux de maladie humaine</term>
<term>Moelle spinale</term>
<term>Muscles</term>
<term>Ossification hétérotopique</term>
<term>Souris de lignée C57BL</term>
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<front><div type="abstract" xml:lang="en"><p>We previously reported the development of a new acquired neurogenic HO (NHO) mouse model, combining spinal cord transection (SCI) and chemical muscle injury. Pathological mechanisms responsible for ectopic osteogenesis after central neurological damage are still to be elucidated. In this study, we first hypothesized that peripheral nervous system (PNS) might convey pathological signals from injured spinal cord to muscles in NHO mouse model. Secondly, we sought to determine whether SCI could lead to intramuscular modifications of BMP2 signaling pathways. Twenty one C57Bl6 mice were included in this protocol. Bilateral cardiotoxin (CTX) injection in hamstring muscles was associated with a two-stage surgical procedure, combining thoracic SCI with unilateral peripheral denervation. Volumes of HO (Bone Volume, BV) were measured 28 days after surgery using micro-computed tomography imaging techniques and histological analyses were made to confirm intramuscular osteogenesis. Volume comparisons were conducted between right and left hind limb of each animal, using a Wilcoxon signed rank test. Quantitative polymerase chain reaction (qPCR) was performed to explore intra muscular expression of BMP2, Alk3 and Id1. Nineteen mice survive the complete SCI and peripheral denervation procedure. When CTX injections were done right after surgery (n = 7), bilateral HO were detected in all animals after 28 days. Micro-CT measurements showed significantly increased BV in denervated paws (1.47 mm3 +/- 0.5) compared to contralateral sides (0.56 mm3 +/-0.4), p = 0.03. When peripheral denervation and CTX injections were performed after sham SCI surgery (n = 6), bilateral HO were present in three mice at day 28. Quantitative PCR analyses showed no changes in intra muscular BMP2 expression after SCI as compared to control mice (shamSCI). Peripheral denervation can be reliably added to spinal cord transection in NHO mouse model. This new experimental design confirms that neuro inflammatory mechanisms induced by central or peripheral nervous system injury plays a key role in triggering ectopic osteogenesis.</p>
</div>
</front>
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