The effect of depression on fracture healing and osteoblast differentiation in rats.
The effect of depression on fracture healing and osteoblast differentiation in rats.
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DOI：
10.2147/ndt.s168653
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发表时间：
2018
影响因子：
3.2
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Nie C;Wang Z;Liu X
抑郁症已被证明与骨代谢紊乱有关。然而，抑郁症对骨折愈合的影响仍缺乏证据。采用蔗糖偏好试验、强迫游泳试验和野外试验对慢性应激大鼠抑郁模型进行了评价。随后，通过显微计算机断层扫描和组织学分析检测股骨髁缺损大鼠有无凹陷的骨修复能力。为了进一步探讨抑郁症对骨折愈合的潜在影响机制，我们比较了抑郁症大鼠和正常大鼠骨髓间充质干细胞（BMSCs）的成骨分化和自噬水平。我们的研究结果显示，抑郁症大鼠在损伤后4周和8周明显减缓了愈合过程。此外，抑郁症大鼠骨髓间充质干细胞的成骨潜能和自噬显著降低，表明自噬与成骨分化之间存在内在关系。最后，自噬激动剂雷帕霉素通过自噬激活显著改善抑制性骨髓间充质干细胞的成骨分化。本研究表明，抑郁对骨折愈合有负面影响，骨髓间充质干细胞成骨细胞分化低。此外，骨髓间充质干细胞的自噬激活为骨折愈合不良的抑郁症患者提供了新的治疗靶点。
Depressive disorder has been proven to be associated with disturbed bone metabolism. However, the effect of depression on fracture healing still lacks evidence. 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. 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. 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.