Interleukin-6 Does Not Contribute to Neurogenic Heterotopic Ossification Pathogenesis
Rattachement africain : fr, au. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Neurogenic heterotopic ossifications (NHOs) are ectopic bones developing in periarticular muscles after severe central nervous system injuries such as spinal cord injuries (SCI) and traumatic brain injuries (TBI). The pathogenesis of NHO is still poorly understood, and the only effective therapy remains surgical resection. Using our unique mouse model of NHO development after SCI and muscle injury, we have previously shown that oncostatin M (OSM), a cytokine of the interleukin-6 (IL-6) superfamily, contributes to NHO pathogenesis. However, a possible role of IL-6 in NHO pathogenesis remains unexplored. Herein, we establish that IL-6 mRNA is significantly upregulated in muscles developing NHO after SCI and that IL-6 protein is significantly elevated in the blood of mice developing NHO. However, administration of anti-IL-6 and anti-IL-6 receptor α chain (IL6RA) neutralizing antibodies after SCI and muscle injury did not impact NHO development. Relevant to the human pathology, recombinant human IL-6 and/or soluble IL-6 receptor α chain (sIL6RA) did not increase the mineralization of human fibro-adipogenic progenitors (FAPs) isolated from muscles surrounding NHO biopsies or the expression of osteoblast genes. As we have previously shown that macrophages are critical for NHO development, we also examined an indirect role of IL-6 on FAPs via peripheral blood monocytes. Results showed that conditioned media from human CD14 + monocytes stimulated with either IL-6 and/or sIL6RA did not increase NHO mineralization or expression of osteoblast genes. Finally, we show that mRNA for IL6RA were expressed at low levels in mesenchymal progenitors isolated from mouse and human muscles compared with OSM receptor α chain and GP130 mRNA which were abundantly expressed by these cells. Overall, our findings suggest that the contribution of the IL-6 pathway to NHO pathogenesis is minimal and that treatment with IL6RA or IL-6 neutralizing antibodies is unlikely to have beneficial effect to stop the development of this pathology.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Interleukin-6 Does Not Contribute to Neurogenic Heterotopic Ossification Pathogenesis
- Date Crossref
- 01/04/2024
- Éditeur
- SAGE Publications
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
Inserm pays non établi dans la noticeOrganisme public
-
Hôpital d'instruction des Armées Percy pays non établi dans la noticeÉtablissement de santé
-
Translational Research Institute pays non établi dans la noticeStructure de recherche
-
The University of Queensland Mater Research Institute pays non établi dans la noticeUniversité ou école supérieure
-
Mater Research pays non établi dans la noticeStructure de recherche
-
Université de Versailles Saint-Quentin-en-Yvelines pays non établi dans la noticeUniversité ou école supérieure
-
Assistance Publique – Hôpitaux de Paris pays non établi dans la noticeÉtablissement de santé
-
Hôpital Raymond-Poincaré pays non établi dans la noticeÉtablissement de santé
-
Institut de Recherche Biomédicale des Armées (IRBA) pays non établi dans la noticeStructure de recherche
-
University of Versailles Saint Quentin en Yvelines UFR Simone Veil-Santé pays non établi dans la noticeUniversité ou école supérieure
-
Raymond-Poincaré Hospital Physical and Rehabilitation Medicine Department pays non établi dans la noticeÉtablissement de santé
Inserm, Hôpital d'instruction des Armées Percy et Translational Research Institute, avec 8 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.