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Interleukin‐1 Is Overexpressed in Injured Muscles Following Spinal Cord Injury and Promotes Neurogenic Heterotopic Ossification
Author(s) -
Tseng HsuWen,
Kulina Irina,
Girard Dorothée,
Gueguen Jules,
Vaquette Cedryck,
Salga Marjorie,
Fleming Whitney,
Jose Beulah,
Millard Susan M,
Pettit Allison R,
Schroder Kate,
Thomas Gethin,
Wheeler Lawrie,
Genêt François,
Banzet Sébastien,
Alexander Kylie A,
Lévesque JeanPierre
Publication year - 2022
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.4482
Subject(s) - inflammation , medicine , heterotopic ossification , tumor necrosis factor alpha , pathology , ossification , spinal cord injury , spinal cord , pathogenesis , cancer research , endocrinology , anatomy , psychiatry
Neurogenic heterotopic ossifications (NHOs) form in periarticular muscles after severe spinal cord (SCI) and traumatic brain injuries. The pathogenesis of NHO is poorly understood with no effective preventive treatment. The only curative treatment remains surgical resection of pathological NHOs. In a mouse model of SCI‐induced NHO that involves a transection of the spinal cord combined with a muscle injury, a differential gene expression analysis revealed that genes involved in inflammation such as interleukin‐1β (IL‐1β) were overexpressed in muscles developing NHO. Using mice knocked‐out for the gene encoding IL‐1 receptor (IL1R1) and neutralizing antibodies for IL‐1α and IL‐1β, we show that IL‐1 signaling contributes to NHO development after SCI in mice. Interestingly, other proteins involved in inflammation that were also overexpressed in muscles developing NHO, such as colony‐stimulating factor‐1, tumor necrosis factor, or C‐C chemokine ligand‐2, did not promote NHO development. Finally, using NHO biopsies from SCI and TBI patients, we show that IL‐1β is expressed by CD68 + macrophages. IL‐1α and IL‐1β produced by activated human monocytes promote calcium mineralization and RUNX2 expression in fibro‐adipogenic progenitors isolated from muscles surrounding NHOs. Altogether, these data suggest that interleukin‐1 promotes NHO development in both humans and mice. © 2021 American Society for Bone and Mineral Research (ASBMR).