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J Musculoskelet Neuronal Interact. 2018 Mar 1;18(1):32-41.

Leptin-deficiency eradicates the positive effect of traumatic brain injury on bone healing: histological analyses in a combined trauma mouse model.

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1
Center for Musculoskeletal Surgery, Charité - University Medicine Berlin, Augustenburger Platz 1, 13353, Berlin, Germany.

Abstract

INTRODUCTION:

The combination of traumatic brain injury (TBI) and long-bone fracture leads to increased formation of callus and mineral density in wild-type (WT) mice. However, this effect was not detected radiologically in leptin-deficient mice. Due to the complex interactions between hormonal and bone metabolism and the important role of leptin in this setting, our aim was to investigate morphologic properties and the tissue composition in the fracture callus comparing WT and leptin-deficient mice.

METHODS:

Female C57/Black6N mice (n=36) and leptin deficient ob/ob mice (n=36) each were assigned to two groups (fracture Fx/combined trauma Fx/TBI). Femoral osteotomy was stabilized with external fixator, TBI was induced with controlled cortical impact injury. After sacrifice of the animals, femora were harvested, cryofixated, and 7 µm slices were prepared. Staining was performed adhering to Movat's Pentachrome protocol. Histomorphometric analysis, quantifying percentage of mineralized bone area, and a semi-quantitative evaluation of bone bridging were performed.

RESULTS:

Leptin deficient mice showed a higher rate of non-union after osteotomy, less callus formation in the osteotomy gap, and unexpected bone and cartilage formation independent of the osteotomy region.

DISCUSSION:

Leptin plays an important role in fracture healing and bone formation. Without Leptin, the positive effect of TBI on fracture healing ceases. The comprehension of the underlying pathophysiological process could sign important for novel strategies in stimulation of fracture healing.

PMID:
29504576
PMCID:
PMC5881126

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