A glucocorticoid spike derails muscle repair to heterotopic ossification after spinal cord injury

被引：3

作者：

Alexander, Kylie A. ^{[1
]}

Tseng, Hsu-Wen ^{[1
]}

Lao, Hong Wa ^{[2
]}

Girard, Dorothee ^{[3
,4
]}

Barbier, Valerie ^{[1
]}

Ungerer, Jacobus P. J. ^{[2
,5
]}

Mcwhinney, Brett C. ^{[5
]}

Samuel, Selwin G. ^{[1
]}

Fleming, Whitney ^{[1
]}

Winkler, Ingrid G. ^{[1
]}

Salga, Marjorie ^{[6
]}

Genet, Francois ^{[6
,7
]}

Banzet, Sebastien ^{[3
,4
]}

Ruitenberg, Marc J. ^{[2
]}

Levesque, Jean-Pierre ^{[1
]}

机构：

[1] Univ Queensland, Mater Res Inst, Translat Res Inst, Woolloongabba, Qld 4102, Australia

[2] Univ Queensland, Fac Med, Sch Biomed Sci, St Lucia, Qld 4067, Australia

[3] Inst Rech Biomed Armees, F-92140 Clamart, France

[4] INSERM, U1197, SToRM, UMR MD, F-92140 Clamart, France

[5] Pathol Queensland, Dept Chem Pathol, Herston, Qld 4029, Australia

[6] Hop Raymond Poincare, APHP, Phys & Rehabil Med Dept, Unite Perioperatoire Handicap, F-92380 Garches, France

[7] Univ Versailles St Quentin En Yvelines, UFR Simone Veil Sante, END ICAP, INSERM,U1179, F-78180 Montigny Le Bretonneux, France

来源：

CELL REPORTS MEDICINE | 2024年 / 5卷 / 12期

基金：

英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;

关键词：

Highlights; severe spinal cord injuries (SCIs) remains; OSTEOBLAST DIFFERENTIATION; TARGETED DISRUPTION; SKELETAL DEVELOPMENT; FRONTAL-CORTEX; BONE-FORMATION; RECEPTOR GENE; MECHANISMS; CELLS; MICE; IDENTIFICATION;

D O I：

10.1016/j.xcrm.2024.101849

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Why severe injury to the central nervous system (CNS) triggers the development of large neurogenic heterotopic ossifications (NHOs) within periarticular muscles remains unknown. We report that spinal cord injury (SCI) triggers a rapid corticosterone spike in mice, which is causal for NHO development because treatments with corticosterone or the synthetic glucocorticoid (GC) receptor (GR) agonist dexamethasone are sufficient to trigger heterotopic ossification and upregulate the expression of osteoinductive and osteogenic differentiation genes in injured muscles even without SCI. The central role for GR signaling in causing NHO is further demonstrated in mice deleted for the GR gene (Nr3c1), which no longer develop NHO after SCI. Furthermore, administration of clinical GR antagonists inhibits NHO development in mice with SCI. This study identifies endogenous GC as causing pathological NHO after CNS injury and suggests that GR antagonists may be of prophylactic use to prevent NHO development in victims of severe CNS injuries.

引用

页数：30

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