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Despite the best treatment, approximately 10% of fractures still face undesirable repair. Recently, many studies have focused on the importance of macrophages in bone repair; however, the cellular mechanisms by which they work are not yet fully understood. In this study, we explored the functions of macrophage G‐protein‐coupled receptor interacting protein 1 (GIT1) in healing a tibial monocortical defect model. Using GIT1flox/flox Lyz2‐Cre (GIT1 CKO) mice, we observed that a GIT1 deficiency in the macrophages led to an exacerbation of interleukin 1β (IL1β) production, more M1‐like macrophage infiltration, and impaired intramembranous ossification in vivo. The results of in vitro assays further indicated that the macrophage GIT1 plays a critical role in several cellular processes in response to lipopolysaccharide (LPS), such as anti‐oxidation, IL1β production alleviation, and glycolysis control. Although GIT1 has been recognized as a scaffold protein, our data clarified that GIT1‐mediated extracellular‐signal‐regulated kinase (ERK) phosphorylation could activate nuclear factor (erythroid‐derived 2)‐like 2 (NRF2) in macrophages after LPS treatment. Moreover, we demonstrated that macrophage GIT1‐activated ERK/NRF2 negatively regulates the 6‐phosphofructo‐2‐kinase/fructose‐2, 6‐biphosphatase 3 (PFKFB3), facilitating the decrease of glycolysis. Our findings uncovered a previously unrecognized role of GIT1 in regulating ERK/NRF2 in macrophages to control the inflammatory response, suggesting that macrophage GIT1 could be a potential target to improve bone regeneration. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.. [ABSTRACT FROM AUTHOR]

Objective: This study aims to examine the biomechanical effects of different reconstruction methods, including single-bundle, double-bundle anatomical reconstruction, and double-bundle truly anatomical reconstruction of the coracoclavicular ligament on the acromioclavicular joint using finite element analysis, to provide a theoretical basis for the clinical application of truly anatomical coracoclavicular ligament reconstruction., Methods: One volunteer, aged 27 years old, with a height of 178 cm and a weight of 75 kg, was selected for CT scanning of the shoulder joint. Three-dimensional finite element models of single-bundle reconstruction, double-bundle anatomical reconstruction, and double-bundle truly anatomical reconstruction of coracoclavicular ligament were established by using Mimics17.0, Geomagic studio 2012, UG NX 10.0, HyperMesh 14.0 and ABAQUS 6.14 software. The maximum displacement of the middle point of the distal clavicle in the main loading direction and the maximum equivalent stress of the reconstruction device under different loading conditions were recorded and compared., Results: The maximum forward displacement and the maximum backward displacement of the middle point of the distal clavicle in the double-bundle truly anatomic reconstruction were the lowest, which were 7.76 mm and 7.27 mm respectively. When an upward load was applied, the maximum displacement of the distal clavicle midpoint in the double-beam anatomic reconstruction was the lowest, which was 5.12 mm. Applying three different loads forward, backward, and upward, the maximum equivalent stress of the reconstruction devices in the double-beam reconstruction was lower than that in the single-beam reconstruction. The maximum equivalent stress of the trapezoid ligament reconstruction device in the double-bundle truly anatomical reconstruction was lower than that in the double-bundle anatomical reconstruction, which was 73.29 MPa, but the maximum equivalent stress of the conoid ligament reconstruction device was higher than that of the double-bundle anatomical reconstruction., Conclusion: The truly anatomical reconstruction of coracoclavicular ligament can improve the horizontal stability of acromioclavicular joint and reduce the stress of the trapezoid ligament reconstruction device. It can be a good method for the treatment of acromioclavicular joint dislocation.

Objectives: To prove the protective effect of Edaravone to neurons and to study the particular mechanism., Methods: Neurons were collected from 18-day fetal rat brains and a culture of almost pure neurons was obtained after 14-day culture, then the cells were randomly assigned to one of the three groups: control group, hydrogen peroxide (H₂O₂)-treated group, and Edaravone-treated group. In H₂O₂-treated group, 300 µmol/L H₂O₂ was added to the medium, followed by returning to the normal culture for the presupposition of time. In Edaravone-treated group, 500 µmol/L Edaravone was prophylactically added to the medium for 30 minutes before the insult. Morphology of mitochondria was visualized by transmission electron microscopy. The rate of apoptotic cells was detected by flow cytometry analysis. The relationships between the proteins and the key proteins expressions were observed by immunoprecipitation and immunoblotting., Results: Compared to the Edaravone-treated group, mitochondria in H₂O₂-treated group displayed more vesicular matrix compartments at the same time. Percentage of apoptotic cells in H₂O₂-treated group after 0.5, 2, 6 and 12 h were 14.40% ± 1.23%, 45.50% ± 2.81%, 56.40% ± 3.53%, 62.50% ± 4.23%, which were higher than control group (F = 274.8, P < 0.01). Edaravone-treated group were 0.90% ± 0.07%, 1.10% ± 0.08%, 3.50% ± 1.90%, 12.60% ± 1.10%, which were lower than H₂O₂-treated group (F = 362.7, P < 0.01). After H₂O₂ stimulation for 0.5 h in H₂O₂-treated group, the levels of p-JNK (Thr183/Tyr185) and cytochrome c in cytosol and BAX in heavy membrane were increased significantly at 0.5 h, reaching a peak at 12 h after stimulation, In addition, the expressions of p-BAD, BAX, BAD and 14-3-3 of cytoplasm decreased, however, these changes were inhibited in the Edaravone-treated group., Conclusions: As a free radical scavenger, the Edaravone could protect neurons by inhibiting the activity of JNK, the disassociation of BAD from 14-3-3 and the translocation of BAX from the cytosol to mitochondria.