桑辛素通过经典 Wnt/β-连环蛋白通路诱导骨髓间充质干细胞的成骨分化，并预防去卵巢大鼠模型的骨丢失。
Morusin induces osteogenic differentiation of bone marrow mesenchymal stem cells by canonical Wnt/β-catenin pathway and prevents bone loss in an ovariectomized rat model.
机构信息
Department of Joint Surgery and Sports medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan, 430071, China.
出版信息
Stem Cell Res Ther. 2021 Mar 12;12(1):173. doi: 10.1186/s13287-021-02239-3.
BACKGROUND
Osteoporosis (OP) is a metabolic bone disease due to the imbalance of osteogenesis and bone resorption, in which, bone marrow mesenchymal stem cells (BMSCs) have a significant effect as the seed cells. Recent research has shown the function of Morusin on inhibiting osteoclast differentiation in vitro. However, whether Morusin can regulate the osteogenic differentiation in addition to the proliferation of BMSCs remains unclear.
METHODS
BMSCs were isolated from 4-week-old Wistar rats and then treated with different concentrations of Morusin for 3, 5, 7, and 14 days. The proliferation of BMSCs was detected by MTT assay. The effect of Morusin on osteogenic differentiation of BMSCs was detected by RT-qPCR, Western blotting, ALP, and Alizarin Red staining. The effect of Morusin on Wnt/β-catenin signaling pathway was analyzed by RT-qPCR, Western blotting, and immunofluorescence. Finally, in the ovariectomy-induced osteoporosis model, the anti-osteoporosis activity of Morusin was determined by micro-CT, HE, and immunohistochemistry.
RESULTS
The results showed the function of 2.5-10 μM Morusin in the promotion of the proliferation in addition to osteogenic differentiation of BMSCs. Moreover, it also has an impact in activating the Wnt/β-catenin signaling pathway via inhibition of β-catenin phosphorylation as well as promotion of its nuclear translocation. Upon Dickkopf-related protein-1 (DKK-1, an inhibitor of the Wnt/β-catenin signaling pathway) was added to the Morusin, Morusin had a decreased stimulatory osteogenic effect on BMSCs. Finally, in the rat OP model, we found that Morusin could also exert anti-osteoporosis activity in vivo.
CONCLUSIONS
This study indicates the ability of Morusin in the promotion of osteogenic differentiation of BMSCs via the activation of Wnt/β-catenin signaling pathway and also shows the potential of Morusin to be an agent for osteoporosis treatment.
背景
骨质疏松症（OP）是一种代谢性骨病，由于成骨和骨吸收之间的失衡，骨髓间充质干细胞（BMSCs）作为种子细胞具有重要作用。最近的研究表明，桑辛素在体外抑制破骨细胞分化方面具有功能。然而，桑辛素除了能调节 BMSCs 的增殖外，是否还能调节成骨分化仍不清楚。
方法
从 4 周龄 Wistar 大鼠中分离出 BMSCs，然后用不同浓度的桑辛素处理 3、5、7 和 14 天。通过 MTT 法检测 BMSCs 的增殖。通过 RT-qPCR、Western blot、碱性磷酸酶（ALP）和茜素红染色检测桑辛素对 BMSCs 成骨分化的影响。通过 RT-qPCR、Western blot 和免疫荧光分析检测桑辛素对 Wnt/β-catenin 信号通路的影响。最后，在卵巢切除诱导的骨质疏松症模型中，通过 micro-CT、HE 和免疫组化测定桑辛素的抗骨质疏松活性。
结果
结果表明，2.5-10μM 桑辛素具有促进 BMSCs 增殖和成骨分化的功能。此外，它还通过抑制β-catenin 磷酸化和促进其核转位来激活 Wnt/β-catenin 信号通路。当向桑辛素中加入 Dickkopf 相关蛋白-1（DKK-1，Wnt/β-catenin 信号通路的抑制剂）时，桑辛素对 BMSCs 的促成骨作用减弱。最后，在大鼠 OP 模型中，我们发现桑辛素在体内也能发挥抗骨质疏松活性。
结论
本研究表明，桑辛素通过激活 Wnt/β-catenin 信号通路促进 BMSCs 的成骨分化，并表明桑辛素具有成为骨质疏松症治疗药物的潜力。
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