ArticlePloS one2017
Peripheral denervation participates in heterotopic ossification in a spinal cord injury model.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- M1 macrophage-derived CXCL12 drives neurogenic heterotopic ossification following spinal cord injury.Neural regeneration research · 2026Article
- Histology of neurogenic heterotopic ossification and comparison with its radiological expression in acute spinal cord injured patients.Spinal cord · 2025Article
- [Research progress of traumatic heterotopic ossification].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2022Review
- Spinal cord injury reprograms muscle fibroadipogenic progenitors to form heterotopic bones within muscles.Bone research · 2022Article
- Review
- Macrophages in heterotopic ossification: from mechanisms to therapy.NPJ Regenerative medicine · 2021Review
- When the Nervous System Turns Skeletal Muscles into Bones: How to Solve the Conundrum of Neurogenic Heterotopic Ossification.Current osteoporosis reports · 2020Review
- Mechanism of traumatic heterotopic ossification: In search of injury-induced osteogenic factors.Journal of cellular and molecular medicine · 2020Review
- Eukarion-134 Attenuates Endoplasmic Reticulum Stress-Induced Mitochondrial Dysfunction in Human Skeletal Muscle Cells.Antioxidants (Basel, Switzerland) · 2020Article
- Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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