Garbe Anja, Graef Frank, Appelt Jessika, Schmidt-Bleek Katharina, Jahn Denise, Lünnemann Tim, Tsitsilonis Serafeim, Seemann Ricarda
Center for Musculoskeletal Surgery, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 13353 Berlin, Germany.
Julius Wolff Institute for Biomechanics and Musculoskeletal Regeneration, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 13353 Berlin, Germany.
Int J Mol Sci. 2020 Nov 30;21(23):9144. doi: 10.3390/ijms21239144.
Recent studies on insulin, leptin, osteocalcin (OCN), and bone remodeling have evoked interest in the interdependence of bone formation and energy household. Accordingly, this study attempts to investigate trauma specific hormone changes in a murine trauma model and its influence on fracture healing. Thereunto 120 female wild type (WT) and leptin-deficient mice underwent either long bone fracture (Fx), traumatic brain injury (TBI), combined trauma (Combined), or neither of it and therefore served as controls (C). Blood samples were taken weekly after trauma and analyzed for insulin and OCN concentrations. Here, WT-mice with Fx and, moreover, with combined trauma showed a greater change in posttraumatic insulin and OCN levels than mice with TBI alone. In the case of leptin-deficiency, insulin changes were still increased after bony lesion, but the posttraumatic OCN was no longer trauma specific. Four weeks after trauma, hormone levels recovered to normal/basal line level in both mouse strains. Thus, WT- and leptin-deficient mice show a trauma specific hyperinsulinaemic stress reaction leading to a reduction in OCN synthesis and release. In WT-mice, this causes a disinhibition and acceleration of fracture healing after combined trauma. In leptin-deficiency, posttraumatic OCN changes are no longer specific and fracture healing is impaired regardless of the preceding trauma.
最近关于胰岛素、瘦素、骨钙素（OCN）和骨重塑的研究引发了人们对骨形成与能量代谢相互依存关系的兴趣。因此，本研究试图在小鼠创伤模型中研究创伤特异性激素变化及其对骨折愈合的影响。为此，120只雌性野生型（WT）和瘦素缺乏小鼠分别接受长骨骨折（Fx）、创伤性脑损伤（TBI）、复合创伤（Combined），或不接受任何创伤，作为对照组（C）。创伤后每周采集血样，分析胰岛素和OCN浓度。在此，发生Fx以及复合创伤的WT小鼠创伤后胰岛素和OCN水平的变化比仅发生TBI的小鼠更大。在瘦素缺乏的情况下，骨损伤后胰岛素变化仍然增加，但创伤后OCN不再具有创伤特异性。创伤后四周，两种小鼠品系的激素水平均恢复到正常/基线水平。因此，WT和瘦素缺乏小鼠表现出创伤特异性高胰岛素应激反应，导致OCN合成和释放减少。在WT小鼠中，这会导致复合创伤后骨折愈合的去抑制和加速。在瘦素缺乏的情况下，创伤后OCN变化不再具有特异性，无论先前的创伤如何，骨折愈合都会受损。
