Puerarin Stimulates Osteogenic Differentiation and Bone Formation Through the ERK1/2 and p38-MAPK Signaling Pathways
Puerarin Stimulates Osteogenic Differentiation and Bone Formation Through the ERK1/2 and p38-MAPK Signaling Pathways
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葛根素通过 ERK1/2 和 p38-MAPK 信号通路刺激成骨分化和骨形成
DOI：
10.2174/1566524018666171219101142
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发表时间：
2017-01-01
影响因子：
2.5
通讯作者：
Jiang, L.
中科院分区：
文献类型：
--
作者：
Yang, X.;Yang, Y.;Jiang, L.
背景：骨质疏松症是一个世界性的健康问题，它会导致骨强度降低，增加骨折的易感性。葛根素是从葛根中提取的一种植物雌激素。Ohwi，已被确定为一种有前途的预防骨丢失和促进骨再生的干预措施。然而，其合成代谢作用的潜在机制仍不清楚。本研究旨在探讨葛根素对骨髓基质细胞(BMSCs)成骨分化的影响及其可能的分子机制。方法：采用骨髓基质细胞(BMSCs)和去卵巢(OVX)大鼠灌胃给药的方法，研究葛根素的抗骨质疏松作用。结果：在最佳浓度下，葛根素可促进BMSCs向成骨方向分化。这种诱导是通过MAPK信号通路介导的。进一步研究发现，在葛根素诱导BMSCs向成骨表型分化过程中，ERK1/2-Runx2信号通路的作用比p38信号通路更为显著。结论：葛根素促进成骨分化的作用机制涉及ERK1/2和p38-MAPK通路，为葛根素在雌激素替代治疗骨质疏松中的应用提供了实验依据。
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.