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葛根素通过ERK1/2和p38丝裂原活化蛋白激酶信号通路刺激成骨分化和骨形成。

Puerarin Stimulates Osteogenic Differentiation and Bone Formation Through the ERK1/2 and p38-MAPK Signaling Pathways.

作者信息

Yang X, Yang Y, Zhou S, Gong X, Dai Q, Zhang P, Jiang L

机构信息

Center of Craniofacial Orthodontics, Department of Oral and Cranio-Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi Zao Ju Road, Shanghai 200011, China.

Department of Pediatric Dentistry, Shanghai 9th People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology; National Clinical Research Center of Stomatology, Shanghai 200011, China.

出版信息

Curr Mol Med. 2018 Mar 9;17(7):488-496. doi: 10.2174/1566524018666171219101142.

Abstract

BACKGROUND

Osteoporosis is a world-wide health problem, which leads to decreased bone strength and increased susceptibility to fractures. Puerarin, a phytoestrogen extracted from Pueraria lobata (Willd.) Ohwi, has been identified as a promising intervention for preventing bone loss and promoting bone regeneration. However, the underlying mechanisms for its anabolic action are still not clear. In the present study, we aimed to investigate the effect of puerarin on the osteogenic differentiation of bone marrow stromal cells (BMSCs) and the possible molecular mechanism mediating its action.

METHODS

Bone marrow stromal cells (BMSCs) and intragastric administration on ovariectomized(OVX) rats were used to study the anti-osteoporotic function of puerarin. The involvement of mitogen-activated protein kinase (MAPK) signaling pathways was determined.

RESULTS

Our results demonstrated that at optimal concentration, puerarin could promote osteogenic differentiation of BMSCs in vitro. This induction was mediated by MAPK signaling pathway. Further detailed study revealed that ERK1/2-Runx2 signaling pathway had more prominent effect than p38 signaling pathway in puerarin-induced differentiation of BMSCs toward the osteogenic phenotype. We also found that puerarin protected against reduction in bone mineral density and improved femur trabecular bone structure in ovariectomized rats.

CONCLUSION

Our findings revealed the functional mechanism of puerarin in promoting osteogenic differentiation which involved ERK1/2 and p38-MAPK pathway and provided experimental evidence for the potential application of puerarin for estrogen replacement therapy of osteoporosis.

摘要

背景

骨质疏松症是一个全球性的健康问题,它会导致骨强度下降以及骨折易感性增加。葛根素是从野葛中提取的一种植物雌激素,已被认为是预防骨质流失和促进骨再生的一种有前景的干预措施。然而,其合成代谢作用的潜在机制仍不清楚。在本研究中,我们旨在研究葛根素对骨髓间充质干细胞(BMSCs)成骨分化的影响及其作用的可能分子机制。

方法

使用骨髓间充质干细胞(BMSCs)和对去卵巢(OVX)大鼠进行灌胃给药来研究葛根素的抗骨质疏松功能。确定丝裂原活化蛋白激酶(MAPK)信号通路的参与情况。

结果

我们的结果表明,在最佳浓度下,葛根素可在体外促进BMSCs的成骨分化。这种诱导是由MAPK信号通路介导的。进一步的详细研究表明,在葛根素诱导BMSCs向成骨表型分化过程中,ERK1/2-Runx2信号通路比p38信号通路具有更显著的作用。我们还发现葛根素可防止去卵巢大鼠骨密度降低,并改善股骨小梁骨结构。

结论

我们的研究结果揭示了葛根素促进成骨分化的功能机制,其涉及ERK1/2和p38-MAPK通路,并为葛根素在骨质疏松症雌激素替代治疗中的潜在应用提供了实验证据。

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