Spinal cord injury dysregulates ﬁbro-adipogenic progenitors miRNAs signaling to promote neurogenic heterotopic ossiﬁcations

Communications Biology, 2023 · DOI: https://doi.org/10.1038/s42003-023-05316-w · Published: September 1, 2023

Spinal Cord Injury Genetics Musculoskeletal Medicine

Simple Explanation

Neurogenic heterotopic ossiﬁcations (NHOs) are extra-skeletal bone formations that occur after central nervous system injury, such as spinal cord injury (SCI). These formations develop at the expense of skeletal muscle tissue, located around major joints and can impair limb mobility. The study found an osteo-suppressive miRNAs response in injured muscle that was hindered when the spinal cord injury was associated. This means that the body's natural mechanism to prevent bone formation in muscles is disrupted by SCI. The overexpression of selected miRNAs in patient’s ﬁbro-adipogenic progenitors inhibited mineralization and osteo-chondrogenic markers in vitro, suggesting miRNAs could be a target for preventing NHOs.

Study Duration

Not specified

Participants

Mice and human muscle progenitor cells from NHOs surgical resection specimens

Evidence Level

Level: Not specified, Study type: In vivo and in vitro study

Key Findings

1
SCI induces mineralization and exacerbates osteo-chondrogenic markers expression in cardiotoxin (CDTX) damaged muscle.
2
Muscle injury triggers osteogenic miRNAs expression while SCI impairs and delays osteo-suppressive miRNAs response after muscle damage.
3
In human FAPs, synthetic miRNAs inhibitors and mimics transfections suppress both mineralization and osteo-chondrogenic markers.

Research Summary

This study investigates the role of miRNAs in neurogenic heterotopic ossiﬁcations (NHOs) following spinal cord injury (SCI) using a mouse model and patient cells. It identifies an osteo-suppressive miRNA response in injured muscle that is impaired by SCI. The research reveals that SCI downregulates osteo-suppressive miRNAs in ﬁbro-adipogenic progenitors (FAPs), cells at the origin of ossiﬁcation, while osteogenic markers are overexpressed. Overexpression of selected miRNAs in patient’s FAPs inhibits mineralization in vitro. The study concludes that SCI disrupts the balance between osteogenic and osteo-suppressive miRNAs, leading to NHOs, and suggests potential preventive treatments targeting these miRNAs.

Practical Implications

Therapeutic Targets

miRNAs identified in this study could be potential therapeutic targets for preventing or treating NHOs in patients with spinal cord injuries.

Preventive Strategies

Understanding the role of miRNAs in NHOs pathogenesis could lead to the development of preventive strategies for individuals at high risk of developing this condition.

Personalized Medicine

miRNA profiles could potentially be used to identify individuals who are more susceptible to developing NHOs, allowing for more personalized treatment approaches.

Study Limitations

1
The study focuses on isolated FAPs and MPs but does not extensively investigate the role of macrophages, which are known key players in NHOs.
2
The complexity of the results suggests a dedicated study is needed to fully understand the role of macrophages in NHOs development and miRNAs signaling.
3
The importance of intercellular miRNAs signaling mechanisms is still debated, requiring further investigation.

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