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Peripheral denervation participates in heterotopic ossification in a spinal cord injury model.

Identifieur interne : 000677 ( PubMed/Curation ); précédent : 000676; suivant : 000678

Peripheral 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'Escalopier [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.

RBID : pubmed:28854256

Descripteurs français

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.

DOI: 10.1371/journal.pone.0182454
PubMed: 28854256

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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>
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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>
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<term>Ossification, Heterotopic (etiology)</term>
<term>Ossification, Heterotopic (pathology)</term>
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<term>Spinal Cord Injuries (diagnostic imaging)</term>
<term>Spinal Cord Injuries (etiology)</term>
<term>Spinal Cord Injuries (pathology)</term>
<term>X-Ray Microtomography</term>
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<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>
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<term>Traumatismes de la moelle épinière (imagerie diagnostique)</term>
<term>Traumatismes de la moelle épinière (étiologie)</term>
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<term>Muscles</term>
<term>Ossification hétérotopique</term>
<term>Traumatismes de la moelle épinière</term>
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<keywords scheme="MESH" qualifier="chemically induced" xml:lang="en"><term>Ossification, Heterotopic</term>
<term>Spinal Cord Injuries</term>
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<term>Spinal Cord</term>
<term>Spinal Cord Injuries</term>
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<term>Spinal Cord</term>
</keywords>
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<term>Spinal Cord Injuries</term>
</keywords>
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<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>
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<term>X-Ray Microtomography</term>
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<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>
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<front><div type="abstract" xml:lang="en">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.</div>
</front>
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<Abstract><AbstractText>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.</AbstractText>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Debaud</LastName>
<ForeName>Charlotte</ForeName>
<Initials>C</Initials>
<Identifier Source="ORCID">http://orcid.org/0000-0002-7859-8415</Identifier>
<AffiliationInfo><Affiliation>Spine Division Orthopaedic Surgery Department, Hôpital Européen Georges Pompidou, APHP, Paris, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>University of Versailles Saint Quentin en Yvelines, U1179 INSERM, UFR des Sciences de la Santé - Simone Veil, Montigny-le-Bretonneux, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Salga</LastName>
<ForeName>Marjorie</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>University of Versailles Saint Quentin en Yvelines, U1179 INSERM, UFR des Sciences de la Santé - Simone Veil, Montigny-le-Bretonneux, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Rehabilitation Service, Hôpital Raymond Poincaré, APHP, CIC-IT 1429, Garches, France.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Begot</LastName>
<ForeName>Laurent</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, France.</Affiliation>
</AffiliationInfo>
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<Author ValidYN="Y"><LastName>Holy</LastName>
<ForeName>Xavier</ForeName>
<Initials>X</Initials>
<AffiliationInfo><Affiliation>Institut de Recherche Biomédicale des Armées, Brétigny-sur-Orge, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Chedik</LastName>
<ForeName>Malha</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>University of Versailles Saint Quentin en Yvelines, U1179 INSERM, UFR des Sciences de la Santé - Simone Veil, Montigny-le-Bretonneux, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>de l'Escalopier</LastName>
<ForeName>Nicolas</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>Orthopaedic Surgery Department, Hôpital d'Instruction des Armées PERCY, Clamart, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Torossian</LastName>
<ForeName>Fréderic</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>University of Paris-Sud, INSERM UMR-S/MD 1197, Hôpital Paul Brousse, APHP, Villejuif, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Levesque</LastName>
<ForeName>Jean-Pierre</ForeName>
<Initials>JP</Initials>
<AffiliationInfo><Affiliation>Blood and Bone Diseases Program, Mater Research Institute, University of Queensland, Woolloongabba and School of Medicine, University of Queensland, Herston, Queensland, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lataillade</LastName>
<ForeName>Jean-Jacques</ForeName>
<Initials>JJ</Initials>
<AffiliationInfo><Affiliation>University of Paris-Sud, Unité mixte Inserm/SSA 1197, IRBA/CTSA/HIA Percy, École du Val de Grâce, Clamart, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Le Bousse-Kerdilès</LastName>
<ForeName>Marie-Caroline</ForeName>
<Initials>MC</Initials>
<AffiliationInfo><Affiliation>University of Paris-Sud, INSERM UMR-S/MD 1197, Hôpital Paul Brousse, APHP, Villejuif, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Genêt</LastName>
<ForeName>François</ForeName>
<Initials>F</Initials>
<AffiliationInfo><Affiliation>University of Versailles Saint Quentin en Yvelines, U1179 INSERM, UFR des Sciences de la Santé - Simone Veil, Montigny-le-Bretonneux, France.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Rehabilitation Service, Hôpital Raymond Poincaré, APHP, CIC-IT 1429, Garches, France.</Affiliation>
</AffiliationInfo>
</Author>
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<Language>eng</Language>
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<ArticleDate DateType="Electronic"><Year>2017</Year>
<Month>08</Month>
<Day>30</Day>
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<MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D055396" MajorTopicYN="N">Bone Morphogenetic Protein 2</DescriptorName>
<QualifierName UI="Q000032" MajorTopicYN="N">analysis</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004179" MajorTopicYN="N">Cobra Cardiotoxin Proteins</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D003714" MajorTopicYN="N">Denervation</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008810" MajorTopicYN="N">Mice, Inbred C57BL</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009132" MajorTopicYN="N">Muscles</DescriptorName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000294" MajorTopicYN="N">innervation</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D009999" MajorTopicYN="N">Ossification, Heterotopic</DescriptorName>
<QualifierName UI="Q000139" MajorTopicYN="N">chemically induced</QualifierName>
<QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName>
<QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013116" MajorTopicYN="N">Spinal Cord</DescriptorName>
<QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName>
<QualifierName UI="Q000187" MajorTopicYN="N">drug effects</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013119" MajorTopicYN="N">Spinal Cord Injuries</DescriptorName>
<QualifierName UI="Q000139" MajorTopicYN="N">chemically induced</QualifierName>
<QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName>
<QualifierName UI="Q000209" MajorTopicYN="N">etiology</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D055114" MajorTopicYN="N">X-Ray Microtomography</DescriptorName>
</MeshHeading>
</MeshHeadingList>
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	Serveur d'exploration sur les relations entre la France et l'Australie
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Peripheral denervation participates in heterotopic ossification in a spinal cord injury model.

Peripheral denervation participates in heterotopic ossification in a spinal cord injury model.

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