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Induced global deletion of glucocorticoid receptor impairs fracture healing

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Item Type:Article
Title:Induced global deletion of glucocorticoid receptor impairs fracture healing
Creators: Rapp, Anna E., Hachemi, Yasmine, Kemmler, Julia, Koenen, Mascha ORCID logoORCID: https://orcid.org/0000-0002-1024-4506, Tuckermann, Jan and Ignatius, Anita
Abstract:Although endogenous glucocorticoids (GCs) are important regulators of bone integrity and the immune system, their role in bone repair after fracture-a process highly dependent on inflammation and bone formation-is unclear. Because most effects of GCs are mediated by the glucocorticoid receptor (GR), we used an inducible global GR knockout (GR(gtROSACreERT2)) mouse model to eliminate endogenous GC action in all cells contributing to bone repair. The healing process was analyzed by cytokine/chemokine multiplex analysis, flow cytometry, histology, gene-expression analysis, microcomputed tomography, and biomechanical analysis. We observed increased early systemic and local inflammatory responses, as well as a significantly higher number of T cells infiltrating the fracture callus. Later in the healing process, we found impaired endochondral ossification in the absence of the GR, leading to persistent cartilage in the calli of the GR(gtROSACreERT2) mice, decreased bending stiffness, and a significantly lower proportion of healed bones. Collectively, our data show that the absence of the GR significantly impairs fracture healing associated with a defective cartilage-to-bone transition, underscoring an important role of GCs during fracture healing.
Keywords:Inflammation, Knockout Mice, Steroids, Bone Repair, Endochondral Ossification, Animals, Mice
Source:FASEB Journal
ISSN:0892-6638
Publisher:Wiley / Federation of American Societies for Experimental Biology
Volume:32
Number:4
Page Range:2235-2245
Date:April 2018
Official Publication:https://doi.org/10.1096/fj.201700459rr
PubMed:View item in PubMed

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