独活寄生汤及其活性成分川芎促进人间充质干细胞的成骨分化并延缓其衰老进程。
Du-Huo-Ji-Sheng-Tang and its active component Ligusticum chuanxiong promote osteogenic differentiation and decrease the aging process of human mesenchymal stem cells.
作者信息
Wang Jir-You, Chen Wei-Ming, Wen Che-Sheng, Hung Shih-Chieh, Chen Pei-Wen, Chiu Jen-Hwey
机构信息
Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC; Department of Orthopedics and Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Department of Orthopedics and Traumatology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
出版信息
J Ethnopharmacol. 2017 Feb 23;198:64-72. doi: 10.1016/j.jep.2016.12.011. Epub 2016 Dec 28.
ETHNOPHARMACOLOGICAL RELEVANCE
Postmenopausal osteoporosis is the most common bone disease worldwide. Information concerning the effects of herbal medicines on mesenchymal cell osteogenesis and senescence remains lacking.
AIM OF THIS STUDY
This study was designed to investigate the effects of Du-Huo-Ji-Sheng-Tang (DHJST), a Chinese herbal medicine and its active component Ligusticum chuanxiong on osteogenic differentiation and the aging process of human mesenchymal cells (hMSCs).
MATERIALS & METHODS: hMSCs were used as in vitro model and osteogenesis was induced by administration of either osteogenesis inducing medium (OIM) or dexamethasone-depleted OIM (DDOIM) for 1-week or 2 weeks and the results were evaluated by measuring the formation of mineralization nodules. The effects of the compound recipe DHJST and its active component L. chuanxiong on hMSCs osteogenesis-related gene expression was determined by real-time PCR that targeted bone morphogenetic protein-2 (BMP2), RUNX2, ALP, COL-1, osteopontin (OPN), and osteocalcin (OCN). Antibodies against BMP-related signaling pathway proteins, such as BMP-2, ERK, SMAD 1/5/8, and RUNX2, were also detected at the protein level by Western blotting. Finally, the cumulative growth curve and senescence of the hMSCs were evaluated in order to assess the aging process.
RESULTS
L. chuanxiong increased osteogenic activity in hMSCs and up-regulated BMP-2 and RUNX2 gene expression via the activation of SMAD 1/5/8 and ERK signaling. Furthermore DHJST also showed a trend towards promoting the same effects in the same system. In the absence of dexamethasone, DHJST did activate SMAD 1/5/8 and ERK signaling and hence increased RUNX2 protein expression in hMSCs. In addition, both DHJST and L. chuanxiong delayed the hMSCs aging process by decreasing cell senescence.
CONCLUSIONS
We concluded that DHJST and its active component L. chuanxiong are able to promote osteogenic activity and decrease hMSCs senescence as cells age.
民族药理学相关性
绝经后骨质疏松症是全球最常见的骨病。关于草药对间充质细胞成骨作用和衰老影响的信息仍然缺乏。
本研究目的
本研究旨在探讨中药独活寄生汤（DHJST）及其活性成分川芎对人间充质细胞（hMSCs）成骨分化和衰老过程的影响。
材料与方法
以hMSCs作为体外模型，通过给予成骨诱导培养基（OIM）或不含地塞米松的OIM（DDOIM）诱导成骨1周或2周，并通过测量矿化结节的形成来评估结果。通过靶向骨形态发生蛋白-2（BMP2）、RUNX2、碱性磷酸酶（ALP）、I型胶原蛋白（COL-1）、骨桥蛋白（OPN）和骨钙素（OCN）的实时PCR来确定复方制剂DHJST及其活性成分川芎对hMSCs成骨相关基因表达的影响。还通过蛋白质印迹法在蛋白质水平检测针对BMP相关信号通路蛋白（如BMP-2、细胞外信号调节激酶（ERK）、SMAD 1/5/8和RUNX2）的抗体。最后，评估hMSCs的累积生长曲线和衰老情况，以评估衰老过程。
结果
川芎通过激活SMAD 1/5/8和ERK信号通路增加hMSCs的成骨活性，并上调BMP-2和RUNX2基因表达。此外，DHJST在同一系统中也显示出促进相同作用的趋势。在没有地塞米松的情况下，DHJST确实激活了SMAD 1/5/8和ERK信号通路，从而增加了hMSCs中RUNX2蛋白的表达。此外，DHJST和川芎均通过降低细胞衰老来延缓hMSCs的衰老过程。
结论
我们得出结论，随着细胞老化，DHJST及其活性成分川芎能够促进成骨活性并降低hMSCs的衰老。
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