Leptin Mediated Pathways Stabilize Posttraumatic Insulin and Osteocalcin Patterns after Long Bone Fracture and Concomitant Traumatic Brain Injury and Thus Influence Fracture Healing in a Combined Murine Trauma Model
Abstract
:1. Introduction
2. Results
2.1. Insulin in WT-Mice
2.2. Osteocalcin in WT-Mice
2.3. Insulin in Leptin-Deficient Mice
2.4. OCN in Leptin-Deficient Mice
2.5. WT-Versus Leptin-Deficient Mice
3. Discussion
4. Materials and Methods
4.1. Experimental Design
4.2. Animal Care and Perioperative Management
4.3. Surgical Procedures
4.4. Blood Sampling
4.5. Hormone Analysis
4.6. Statistical Analysis
Author Contributions
Funding
Conflicts of Interest
Abbreviations
OCN | Osteocalcin |
WT | Wild-Type |
Fx | Fracture |
TBI | Traumatic Brain Injury |
Combined | Combined Trauma |
C | Control |
KO | Knock-Out |
ECM | Extra Cellular Matrix |
SNS | Sympathetic Nervous System |
ESP | Embryonic-Stem-Cell-Phosphatase |
OST-PTP | Osteoblast Testicular Tyrosinphosphatase |
FoxO-1 | Forkhead Box Protein O-1 |
OPG | Ostoeprotegrin |
Runx 2 | Runt-Related Transcription Factor 2 |
RANK | Receptor Activator of NF-κB |
RANKL | Receptor Activator of NF-κB-Ligand |
ANOVA | Analysis of Variance |
pg | Picogram |
mL | Milliliter |
CT | Computer Tomography |
CNS | Central Nervous System |
BMD | Bone Mineral Density |
BM | Bone Mass |
BBB | Blood Brain Barrier |
IL | Interleukin |
CCII | Controlled Cortical Impact Injury |
n | Number |
ELISA | Enzyme Linked Immuno Sorbent Assay |
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Fracture | TBI | Combined | Control | ||
---|---|---|---|---|---|
Insulin 2 Hours | Median in pg/mL | 177 | 162 | 237 | 142 |
Interquartile Range in pg/mL | 106 | 115 | 137 | 146 | |
Insulin 1 Week | Median in pg/mL | 189 | 148.5 | 225 | 138 |
Interquartile Range in pg/mL | 138 | 159 | 84 | 240 | |
Insulin 2 Weeks | Median in pg/mL | 211.5 | 234 | 252 | 85.5 |
Interquartile Range in pg/mL | 176 | 423 | 210 | 71 | |
Insulin 3 Weeks | Median in pg/mL | 113 | 127.5 | 229.5 | 117.5 |
Interquartile Range in pg/mL | 124 | 171 | 241 | 98 | |
Insulin 4 Weeks | Median in pg/mL | 102 | 229 | 138 | 167 |
Interquartile Range in pg/mL | 180 | 153 | 33 | 47 |
Fracture | TBI | Combined | Control | ||
---|---|---|---|---|---|
OCN 2 Hours | Median in pg/mL | 50,064 | 49,638 | 51,891 | 46,701 |
Interquartile Range in pg/mL | 22,098 | 27,636 | 21,870 | 21,951 | |
OCN 1 Week | Median in pg/mL | 34,263 | 39,078 | 27,711 | 38,490 |
Interquartile Range in pg/mL | 14,703 | 24,588 | 14,965 | 16,536 | |
OCN 2 Weeks | Median in pg/mL | 41,892 | 61,596 | 29,733 | 43,104 |
Interquartile Rangein pg/mL | 10,686 | 44,613 | 23,728 | 16,818 | |
OCN 3 Weeks | Median in pg/mL | 42,093 | 68,655 | 55,104 | 51,717 |
Interquartile Range in pg/mL | 13,593 | 16,605 | 35,964 | 22,371 | |
OCN 4 Weeks | Median in pg/mL | 53,106 | 44,862 | 64,470 | 55,719 |
Interquartile Rangein pg/mL | 24,728 | 30,109 | 36,600 | 16,362 |
Fracture | TBI | Combined | Control | ||
---|---|---|---|---|---|
Insulin 2 Hours | Median in pg/mL | 21,320 | 33,472 | 19,064 | 19,026 |
Interquartile Range in pg/mL | 14,484 | 26,935 | 16,096 | 49,030 | |
Insulin 1 Week | Median in pg/mL | 82,188 | 47,934 | 25,536 | 66,022 |
Interquartile Range in pg/mL | 84,972 | 44,307 | 73,852 | 53,700 | |
Insulin 2 Weeks | Median in pg/mL | 30,419 | 84,300 | 62,772 | 36,444 |
Interquartile Range in pg/mL | 31,299 | 62,324 | 88,050 | 24,174 | |
Insulin 3 Weeks | Median in pg/mL | 3058 | 28,572 | 3992 | 17,760 |
Interquartile Range in pg/mL | 11,615.5 | 74,414 | 6104 | 13,398 | |
Insulin 4 Weeks | Median in pg/mL | 1204 | 6396 | 2177.5 | 10,825 |
Interquartile Range in pg/mL | 1309.5 | 3407 | 1683.5 | 10,025 |
Fracture | TBI | Combined | Control | ||
---|---|---|---|---|---|
OCN 2 Hours | Median in pg/mL | 36,669 | 39,258 | 40,236 | 32,046 |
Interquartile Range in pg/mL | 21,219 | 19,158 | 28,836 | 22,068 | |
OCN 1 Week | Median in pg/mL | 9030 | 6416 | 7761 | 25,803 |
Interquartile Range in pg/mL | 9051 | 8339 | 1284 | 17,713.5 | |
OCN 2 Weeks | Median in pg/mL | 11,255 | 10,334 | 10,376 | 26,370 |
Interquartile Range in pg/mL | 5901 | 10,270 | 8772 | 20,022 | |
OCN 3 Weeks | Median in pg/mL | 40,365 | 28,419 | 43,098 | 41,238 |
Interquartile Range in pg/mL | 30,585 | 24,532.5 | 42,006 | 18,667.5 | |
OCN 4 Weeks | Median in pg/mL | 46,320 | 47,280 | 47,334 | 68,631 |
Interquartile Range in pg/mL | 14,170 | 4149 | 24,642 | 5623.5 |
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Garbe, A.; Graef, F.; Appelt, J.; Schmidt-Bleek, K.; Jahn, D.; Lünnemann, T.; Tsitsilonis, S.; Seemann, R. Leptin Mediated Pathways Stabilize Posttraumatic Insulin and Osteocalcin Patterns after Long Bone Fracture and Concomitant Traumatic Brain Injury and Thus Influence Fracture Healing in a Combined Murine Trauma Model. Int. J. Mol. Sci. 2020, 21, 9144. https://doi.org/10.3390/ijms21239144
Garbe A, Graef F, Appelt J, Schmidt-Bleek K, Jahn D, Lünnemann T, Tsitsilonis S, Seemann R. Leptin Mediated Pathways Stabilize Posttraumatic Insulin and Osteocalcin Patterns after Long Bone Fracture and Concomitant Traumatic Brain Injury and Thus Influence Fracture Healing in a Combined Murine Trauma Model. International Journal of Molecular Sciences. 2020; 21(23):9144. https://doi.org/10.3390/ijms21239144
Chicago/Turabian StyleGarbe, Anja, Frank Graef, Jessika Appelt, Katharina Schmidt-Bleek, Denise Jahn, Tim Lünnemann, Serafeim Tsitsilonis, and Ricarda Seemann. 2020. "Leptin Mediated Pathways Stabilize Posttraumatic Insulin and Osteocalcin Patterns after Long Bone Fracture and Concomitant Traumatic Brain Injury and Thus Influence Fracture Healing in a Combined Murine Trauma Model" International Journal of Molecular Sciences 21, no. 23: 9144. https://doi.org/10.3390/ijms21239144