Hai-Xiang Xiao, Lei Yu, Yu Xia, Kai Chen, Wen-Ming Li, Gao-Ran Ge, Wei Zhang, Qing Zhang, Hong-Tao Zhang, De-Chun Geng
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引用次数: 0
摘要
背景 骨髓间充质基质细胞(BMSCs)自噬能力下降被认为是成骨分化能力下降的一个重要原因。通过药物增加骨髓间充质基质细胞的自噬能力是提高成骨细胞活力和改善骨质疏松症的一种潜在治疗方法。目的 探讨西诺明(SIN)对 BMSCs 成骨分化的影响及其内在机制。方法 在体外实验中,从假性治疗小鼠和卵巢切除小鼠体内提取 BMSCs,用适当浓度的 SIN 和自噬抑制剂 3-甲基腺嘌呤处理后,检测自噬标记物的水平和成骨分化情况。在体内,通过建立卵巢切除诱导的小鼠模型以及对小鼠股骨进行形态学和组织学检测,验证了 SIN 的治疗效果。结果 SIN 能降低磷脂酰肌醇 3- 激酶(PI3K)/AKT/mTOR 信号通路中 AKT 和哺乳动物雷帕霉素靶标(mTOR)的磷酸化水平,抑制 mTOR 活性,提高 BMSCs 的自噬能力,从而促进 BMSCs 的成骨分化,有效缓解卵巢切除小鼠体内的骨质流失。结论 中药 SIN 具有治疗各类骨质疏松症、骨平衡失调和自噬相关疾病的潜力。
Sinomenine increases osteogenesis in mice with ovariectomy-induced bone loss by modulating autophagy
BACKGROUND
A decreased autophagic capacity of bone marrow mesenchymal stromal cells (BMSCs) has been suggested to be an important cause of decreased osteogenic differentiation. A pharmacological increase in autophagy of BMSCs is a potential therapeutic option to increase osteoblast viability and ameliorate osteoporosis.
AIM
To explore the effects of sinomenine (SIN) on the osteogenic differentiation of BMSCs and the underlying mechanisms.
METHODS
For in vitro experiments, BMSCs were extracted from sham-treated mice and ovariectomized mice, and the levels of autophagy markers and osteogenic differentiation were examined after treatment with the appropriate concentrations of SIN and the autophagy inhibitor 3-methyladenine. In vivo , the therapeutic effect of SIN was verified by establishing an ovariectomy-induced mouse model and by morphological and histological assays of the mouse femur.
RESULTS
SIN reduced the levels of AKT and mammalian target of the rapamycin (mTOR) phosphorylation in the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR signaling pathway, inhibited mTOR activity, and increased autophagy ability of BMSCs, thereby promoting the osteogenic differentiation of BMSCs and effectively alleviating bone loss in ovariectomized mice in vivo .
CONCLUSION
The Chinese medicine SIN has potential for the treatment of various types of osteoporosis, bone homeostasis disorders, and autophagy-related diseases.
期刊介绍:
The World Journal of Stem Cells (WJSC) is a leading academic journal devoted to reporting the latest, cutting-edge research progress and findings of basic research and clinical practice in the field of stem cells. It was launched on December 31, 2009 and is published monthly (12 issues annually) by BPG, the world''s leading professional clinical medical journal publishing company.