Osthole improves therapy for osteoporosis through increasing autophagy of mesenchymal stem cells
Osthole improves therapy for osteoporosis through increasing autophagy of mesenchymal stem cells
复制标题
蛇床子素通过增加间充质干细胞的自噬改善骨质疏松症的治疗
DOI：
10.1538/expanim.18-0178
复制
发表时间：
2019-01-01
影响因子：
2.4
通讯作者：
Yang, Deqin
中科院分区：
文献类型：
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作者：
Zheng, Xuedan;Yu, Yang;Yang, Deqin
骨质疏松症是一种常见的骨骼疾病，导致骨折风险升高。改善成骨分化被认为是骨质疏松症治疗项目的重中之重。骨髓间充质干细胞（BMMSCs）的显著特性，特别是向成骨细胞分化的吸引力，使其成为骨质疏松症治疗的替代选择。然而，BMMSCs的治疗效果仍有待提高。本研究将从多种药用植物中提取的具有生物活性的简单香豆素衍生物蛇耳素引入预刺激BMMSCs，然后应用于骨质疏松症的治疗。结果显示，osthole-treated-BMMSCs （OBMMSCs）在雌激素缺乏性骨质疏松模型中的治疗效果优于单独使用BMMSCs。自噬水平升高可能是蛇耳素促进成骨细胞分化的潜在机制，其机制可以通过上调自噬相关基因Beclin1和LC3的蛋白和mRNA表达水平来体现。我们从这些实验中得出结论，OBMMSCs比BMMSCs更有效地治疗骨质疏松症，可能是通过上调蛇床子素诱导的自噬水平。
Osteoporosis is a common skeletal disorder resulting in elevated fracture risk. Improvement of osteogenic differentiation is thought to be the top priority in osteoporosis treatment projects. Significant characteristics of bone marrow mesenchymal stem cells (BMMSCs), especially attractive ability to differentiate into osteoblasts, have made them alternatives for osteoporosis treatment. However, therapeutic effect with BMMSCs remains to be improved. Here, osthole, a bioactive simple coumarin derivative extracted from many medicinal plants, was introduced to pre-stimulate BMMSCs and then applied in osteoporosis therapy. The results showed that osthole-treated-BMMSCs (OBMMSCs) brought a better outcome than BMMSCs alone in estrogen deficiency-induced osteoporosis model. And elevated autophagy level was suggested to be the underlying mechanism of the ability of osthole to promote osteoblast differentiation, which is indicated by the upregulation of protein and mRNA expression level of autophagy-associated genes, Beclin1 and LC3. We concluded from these experiments that OBMMSCs are more effective than BMMSCs in osteoporosis treatment maybe through upregulation level of autophagy level induced by osthole.