| Summary: | Chunzi Nie,1 Zhan Wang,2 Xufeng Liu1 1Department of Military Medical Psychology, Fourth Military Medical University, Xi’an 710032, People’s Republic of China; 2Department of Orthopaedics, Gansu Provincial Hospital, Lanzhou, Gansu 730050, People’s Republic of China Background: Depressive disorder has been proven to be associated with disturbed bone metabolism. However, the effect of depression on fracture healing still lacks evidence. Materials and methods: A rat depressive model was first established by exposing the animals to chronic unpredictable stress, which was assessed using the sucrose preference test, forced swimming test, and open field test. Subsequently, the bone repairing ability was detected by micro-computed tomography and histological analysis of the femoral condyle defect rats with or without depression. To further investigate the potential mechanisms of depression on fracture healing, the osteogenic differentiation and autophagic level were compared between the bone marrow mesenchymal stem cells (BMSCs) derived from depressive and normal rats. Results: Our results showed that rats with depressive disorder significantly slowed the healing process at 4 and 8 weeks postinjury. Furthermore, the osteogenic potential and autophagy remarkably decreased in BMSCs from the depressive rats, suggesting an inherent relationship between autophagy and osteogenic differentiation. Finally, rapamycin, an autophagic agonist, significantly improved osteogenic differentiation of depressive BMSCs through autophagy activation. Conclusion: The present study indicated that depression had a negative effect on fracture healing with low osteoblast differentiation of BMSCs. Also, autophagy activation in BMSCs offers a novel therapeutic target for depressive patients with poor fracture healing. Keywords: depression, fracture healing, osteoblast differentiation, autophagy, bone marrow mesenchymal stem cells
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