Intact Glucocorticoid Receptor Dimerization Is Deleterious in Trauma-Induced Impaired Fracture Healing.
| Autor: | Hachemi Y; Institute of Comparative Molecular Endocrinology, Ulm University, Ulm, Germany., Rapp AE; Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, Ulm, Germany., Lee S; Institute of Comparative Molecular Endocrinology, Ulm University, Ulm, Germany., Dorn AK; Institute of Comparative Molecular Endocrinology, Ulm University, Ulm, Germany., Krüger BT; Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, Ulm, Germany., Kaiser K; Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, Ulm, Germany., Ignatius A; Institute of Orthopedic Research and Biomechanics, Ulm University Medical Center, Ulm, Germany., Tuckermann J; Institute of Comparative Molecular Endocrinology, Ulm University, Ulm, Germany. |
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| Jazyk: | angličtina |
| Zdroj: | Frontiers in immunology [Front Immunol] 2021 Feb 17; Vol. 11, pp. 628287. Date of Electronic Publication: 2021 Feb 17 (Print Publication: 2020). |
| DOI: | 10.3389/fimmu.2020.628287 |
| Abstrakt: | Following severe trauma, fracture healing is impaired because of overwhelming systemic and local inflammation. Glucocorticoids (GCs), acting via the glucocorticoid receptor (GR), influence fracture healing by modulating the trauma-induced immune response. GR dimerization-dependent gene regulation is essential for the anti-inflammatory effects of GCs. Therefore, we investigated in a murine trauma model of combined femur fracture and thoracic trauma, whether effective GR dimerization influences the pathomechanisms of trauma-induced compromised fracture healing. To this end, we used mice with decreased GR dimerization ability (GR dim ). The healing process was analyzed by cytokine/chemokine multiplex analysis, flow cytometry, gene-expression analysis, histomorphometry, micro-computed tomography, and biomechanical testing. GR dim mice did not display a systemic or local hyper-inflammation upon combined fracture and thorax trauma. Strikingly, we discovered that GR dim mice were protected from fracture healing impairment induced by the additional thorax trauma. Collectively and in contrast to previous studies describing the beneficial effects of intact GR dimerization in inflammatory models, we report here an adverse role of intact GR dimerization in trauma-induced compromised fracture healing. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Hachemi, Rapp, Lee, Dorn, Krüger, Kaiser, Ignatius and Tuckermann.) |
| Databáze: | MEDLINE |
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