1. Peripheral denervation participates in heterotopic ossification in a spinal cord injury model
- Author
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François Genêt, Marie-Caroline Le Bousse-Kerdilès, Malha Chedik, Frédéric Torossian, Nicolas de l’Escalopier, Jean-Jacques Lataillade, Xavier Holy, Laurent Begot, Charlotte Debaud, Jean-Pierre Levesque, and Marjorie Salga
- Subjects
0301 basic medicine ,Pathology ,Cell signaling ,Critical Care and Emergency Medicine ,Physiology ,lcsh:Medicine ,Bone Morphogenetic Protein 2 ,Cobra Cardiotoxin Proteins ,Hindlimb ,Ossification ,Signal transduction ,Nervous System ,0302 clinical medicine ,Medicine and Health Sciences ,Medicine ,Orthopedics and Sports Medicine ,lcsh:Science ,Spinal Cord Injury ,Spinal cord injury ,Trauma Medicine ,Denervation ,Multidisciplinary ,Nerves ,Muscles ,Rehabilitation ,Animal Models ,Peripheral ,medicine.anatomical_structure ,Spinal Cord ,Neurology ,Experimental Organism Systems ,Peripheral nervous system ,Female ,Bone Remodeling ,medicine.symptom ,Anatomy ,Traumatic Injury ,Research Article ,medicine.medical_specialty ,Cell biology ,BMP signaling ,Mouse Models ,Surgical and Invasive Medical Procedures ,Research and Analysis Methods ,03 medical and health sciences ,Sciatic Nerves ,Cardiotoxin ,Model Organisms ,Animals ,Spinal Cord Injuries ,business.industry ,Ossification, Heterotopic ,lcsh:R ,Biology and Life Sciences ,X-Ray Microtomography ,medicine.disease ,Spinal cord ,Mice, Inbred C57BL ,Disease Models, Animal ,Neuroanatomy ,030104 developmental biology ,lcsh:Q ,Heterotopic ossification ,business ,Physiological Processes ,Neurotrauma ,030217 neurology & neurosurgery ,Neuroscience - Abstract
Introduction/Background 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. Secondly, we sought to determine whether SCI could lead to intramuscular modifications of BMP2 signalling pathways. Material and method 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. Results 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. qPCR analyses showed no changes in intra muscular BMP2 expression after SCI as compared to control mice. Conclusion 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.
- Published
- 2017