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

摘要

Introduction: The combination of traumatic brain injury (TBI) and long-bone fracture leads to increased formation of callusand mineral density in wild-type (WT) mice. However, this effect was not detected radiologically in leptin-deficient mice. Dueto the complex interactions between hormonal and bone metabolism and the important role of leptin in this setting, ouraim was to investigate morphologic properties and the tissue composition in the fracture callus comparing WT and leptindeficientmice. Methods: Female C57/Black6N mice (n=36) and leptin deficient ob/ob mice (n=36) each were assigned totwo groups (fracture Fx/combined trauma Fx/TBI). Femoral osteotomy was stabilized with external fixator, TBI was inducedwith controlled cortical impact injury. After sacrifice of the animals, femora were harvested, cryofixated, and 7 μm sliceswere prepared. Staining was performed adhering to Movat’s Pentachrome protocol. Histomorphometric analysis, quantifyingpercentage of mineralized bone area, and a semi-quantitative evaluation of bone bridging were performed. Results: Leptindeficient mice showed a higher rate of non-union after osteotomy, less callus formation in the osteotomy gap, and unexpectedbone and cartilage formation independent of the osteotomy region. Discussion: Leptin plays an important role in fracturehealing and bone formation. Without Leptin, the positive effect of TBI on fracture healing ceases. The comprehension of theunderlying pathophysiological process could sign important for novel strategies in stimulation of fracture healing.