Impaired fracture healing with high non-union rates remains irreversible after traumatic brain injury in leptin-deficient mice
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Impaired fracture healing with high non-union rates remains irreversible after traumatic brain injury in leptin-deficient mice. / Graef, F; Seemann, R; Garbe, A; Schmidt-Bleek, K; Schaser, K D; Keller, Johannes; Duda, G; Tsitsilonis, S.
In: J MUSCULOSKEL NEURON, Vol. 17, No. 2, 01.06.2017, p. 78-85.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Impaired fracture healing with high non-union rates remains irreversible after traumatic brain injury in leptin-deficient mice
AU - Graef, F
AU - Seemann, R
AU - Garbe, A
AU - Schmidt-Bleek, K
AU - Schaser, K D
AU - Keller, Johannes
AU - Duda, G
AU - Tsitsilonis, S
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Patients with traumatic brain injury (TBI) and long-bone fractures can show increased callus formation. This effect has already been reproduced in wild-type (wt) mice. However, the mechanisms remain poorly understood. Leptin is significantly increased following TBI, while its role in bone healing remains unclear. The aim of this study was to evaluate fracture healing in leptin-deficient ob/ob mice and to measure any possible impact of TBI on callus formation. 138 female, 12 weeks old, ob/ob mice were divided into four groups: Control, fracture, TBI and combined trauma. Osteotomies were stabilized with an external fixator; TBI was induced with Controlled Cortical Impact Injury. Callus bridging was weekly evaluated with in vivo micro-CT. Biomechanical testing was performed ex vivo. Micro-CT showed high non-union rates after three and four weeks in the fracture and combined trauma group. No differences were observed in callus volume, density and biomechanical properties at any time point. This study shows that bony bridging is impaired in the present leptin-deficient trauma model. Furthermore, the phenomenon of increased callus formation after TBI could not be reproduced in ob/ob mice, as in wt mice. Our findings suggest that the increased callus formation after TBI may be dependent on leptin signaling.
AB - Patients with traumatic brain injury (TBI) and long-bone fractures can show increased callus formation. This effect has already been reproduced in wild-type (wt) mice. However, the mechanisms remain poorly understood. Leptin is significantly increased following TBI, while its role in bone healing remains unclear. The aim of this study was to evaluate fracture healing in leptin-deficient ob/ob mice and to measure any possible impact of TBI on callus formation. 138 female, 12 weeks old, ob/ob mice were divided into four groups: Control, fracture, TBI and combined trauma. Osteotomies were stabilized with an external fixator; TBI was induced with Controlled Cortical Impact Injury. Callus bridging was weekly evaluated with in vivo micro-CT. Biomechanical testing was performed ex vivo. Micro-CT showed high non-union rates after three and four weeks in the fracture and combined trauma group. No differences were observed in callus volume, density and biomechanical properties at any time point. This study shows that bony bridging is impaired in the present leptin-deficient trauma model. Furthermore, the phenomenon of increased callus formation after TBI could not be reproduced in ob/ob mice, as in wt mice. Our findings suggest that the increased callus formation after TBI may be dependent on leptin signaling.
KW - Animals
KW - Bony Callus/metabolism
KW - Brain Injuries, Traumatic/metabolism
KW - Female
KW - Femoral Fractures/metabolism
KW - Fracture Healing/physiology
KW - Leptin/deficiency
KW - Mice
KW - Mice, Obese
KW - Random Allocation
M3 - SCORING: Journal article
C2 - 28574414
VL - 17
SP - 78
EP - 85
IS - 2
ER -