Influence of Menopause on Inflammatory Cytokines during Murine and Human Bone Fracture Healing
Abstract
:1. Introduction
2. Results
2.1. Inflammatory Response to Fracture in Mice
2.1.1. Increase in Systemic Mdk Concentrations in Estrogen-Deficient Mice after Fracture
2.1.2. Increase in Mdk and IL-6 Concentrations in The Fracture Hematoma of Estrogen-Deficient Mice after Fracture
2.2. Inflammatory Response to Fracture in Humans
2.2.1. Increase in Systemic Mdk Concentrations in Female Fracture Patients after Menopause
2.2.2. Systemic IL-6 and CRP Concentrations in Female Fracture Patients after Menopause
2.2.3. Effects of Fracture Sera on Osteogenic Differentiation of Human MSCs
3. Discussion
4. Materials and Methods
4.1. Evaluation of The Inflammatory Response to Fracture in Mice
4.1.1. Experimental Study Design
4.1.2. Ovariectomy and Osteotomy Surgeries
4.1.3. Cytokine and Chemokine Analyses in Blood Plasma and Fracture Hematoma
4.2. Evaluation of The Inflammatory Response to Fracture in Humans
4.2.1. Clinical Study Design
4.2.2. Blood Samples
4.2.3. ELISAs
4.3. Evaluation of The Effects of Fracture Sera on Human MSCs In Vitro
4.3.1. Cell-Culture Experiments
4.3.2. qPCR
4.4. Statistical Analysis
5. Conclusions
6. Patents
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ANOVA | Analysis of variance |
ALPL | Alkaline phosphatase |
BCA | Bicinchoninic acid |
BGLAP | Bone gamma-carboxyglutamate protein |
COL1 | Collagen-1 |
CRP | C-reactive protein |
Ctl | Control |
CXCL-1 | Chemokine (C-X-C motif) ligand-1 |
ELISA | Enzyme-linked immunosorbent assay |
Fx | Fracture |
GAPDH | Glyceraldehyde-3-phosphate dehydrogenase |
IBSP | Integrin-binding sialoprotein |
IL | Interleukin |
MCP-1 | Monocyte chemoattractant protein-1 |
Mdk | Midkine |
Mdk-Ab | Midkine-antibody |
MIP-1α | Macrophage inflammatory protein-1α |
MSC | Mesenchymal stem cell |
ND | Non-detected |
OVX | Ovariectomized |
qPCR | Quantitative polymerase chain reaction |
RNA | Ribonucleic acid |
RUNX2 | Runt-related transcription factor 2 |
TNF-α | Tumor necrosis factor-α |
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Fischer, V.; Kalbitz, M.; Müller-Graf, F.; Gebhard, F.; Ignatius, A.; Liedert, A.; Haffner-Luntzer, M. Influence of Menopause on Inflammatory Cytokines during Murine and Human Bone Fracture Healing. Int. J. Mol. Sci. 2018, 19, 2070. https://doi.org/10.3390/ijms19072070
Fischer V, Kalbitz M, Müller-Graf F, Gebhard F, Ignatius A, Liedert A, Haffner-Luntzer M. Influence of Menopause on Inflammatory Cytokines during Murine and Human Bone Fracture Healing. International Journal of Molecular Sciences. 2018; 19(7):2070. https://doi.org/10.3390/ijms19072070
Chicago/Turabian StyleFischer, Verena, Miriam Kalbitz, Fabian Müller-Graf, Florian Gebhard, Anita Ignatius, Astrid Liedert, and Melanie Haffner-Luntzer. 2018. "Influence of Menopause on Inflammatory Cytokines during Murine and Human Bone Fracture Healing" International Journal of Molecular Sciences 19, no. 7: 2070. https://doi.org/10.3390/ijms19072070