Rapamycin facilitates fracture healing through inducing cell autophagy and suppressing cell apoptosis in bone tissues

Z.-Y. Yin, J. Yin, Y.-F. Huo, J. Yu, L.-X. Sheng, Y.-F. Dong

Department of Orthopedics, the Affiliated Lianyungang Hospital of Xuzhou Medical University, The First People’s Hospital of Lianyungang, Lianyungang, China. dongyuefu@163.com

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• Pharmacology

OBJECTIVE: To investigate the changes in cell autophagy and the molecular mechanism of rapamycin affecting the fracture healing.

MATERIAL AND METHODS: Sprague-Dawley (SD) rats were used to establish the right femoral shaft fracture models, and then underwent immunofluorescence assay to detect the autophagy level in bone tissues. After model establishment, SD rats were divided into two groups, the control group and the rapamycin group (1 mg/kg/d). Respectively, at the 2nd, 4th, and 6th week, rats were randomly selected from each group for X-ray and Micro-computed tomography (Micro-CT) examinations to determine callus growth, immunofluorescence assay to detect the protein expression of light chain 3 II (LC3 II), immunohistochemistry to evaluate the autophagy level through detecting the expression of Beclin1 in rats, Western blotting assay to detect cell apoptosis in tissues, hematoxylin and eosin staining (HE staining) to evaluate the osteoblastic activity through count of osteoblast in bone tissue at the end of fracture, and measure the expression of vascular endothelial growth factors (VEGF).

RESULTS: Significant increases were seen in protein expression of cells in bone tissues at the end of fracture. In rapamycin group, callus formation and calcification level in rats were all higher than those in control group; compared with control group, for rats in rapamycin group, cell autophagy was significantly elevated in bone tissues, while cell apoptosis at the end of fracture was reduced with a significant increase in osteoblastic activity. The expression of VEGF in rapamycin group was higher than that in control group.

CONCLUSIONS: Rapamycin can facilitate fracture healing through inducing cell apoptosis and suppressing cell apoptosis in bone tissues.

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