Imperatorin promotes osteogenesis and suppresses osteoclast by activating AKT/GSK3 beta/beta-catenin pathways
Imperatorin promotes osteogenesis and suppresses osteoclast by activating AKT/GSK3 beta/beta-catenin pathways
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欧前胡素通过激活 AKT/GSK3 β/β-连环蛋白途径促进成骨并抑制破骨细胞
DOI：
10.1111/jcmm.14915
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发表时间：
2020
影响因子：
5.3
通讯作者：
Yang Lei
中科院分区：
文献类型：
--
作者：
Yan De-Yi;Tang Jiahao;Chen Liang;Wang Bingzhang;Weng Sheji;Xie Zhongjie;Wu Zong-Yi;Shen Zijian;Bai Bingli;Yang Lei
骨质疏松症是由骨重建的动态平衡紊乱引起的，骨重建是一种生理过程，对于维持成年人的健康骨组织至关重要。在这个过程中，成骨细胞形成新骨，破骨细胞吸收预先存在的骨基质。欧前胡素是一种广泛使用的廉价植物提取物，具有抗氧化和凋亡作用，据报道可治疗骨质疏松症。然而，对骨代谢的潜在机制和具体影响尚未阐明。在这项研究中，我们使用大鼠骨髓间充质干细胞，发现欧前胡素可以通过促进GSK 3 β的Ser 9磷酸化和β-catenin进入细胞核来激活RUNX 2，COL 1A 1和骨钙素。欧前胡素还增强了磷酸化AKT（Ser 473）的产生，这是一种促进GSK 3 β Ser 9磷酸化的上游因子。我们使用ipatasertib（一种泛AKT抑制剂）抑制欧前胡素的成骨作用，发现欧前胡素通过AKT/GSK 3 β/β-catenin途径促进成骨。接下来，我们使用大鼠骨髓来源的单核细胞来检查欧前胡素是否通过AKT/GSK 3 β/β-catenin途径抑制破骨细胞分化。进一步切除大鼠双侧卵巢建立卵巢癌模型。欧前胡素灌胃促进体内成骨细胞的形成，抑制破骨细胞的形成。我们的实验表明，欧前胡素是一种潜在的骨质疏松症治疗药物。
Osteoporosis is caused by disturbance in the dynamic balance of bone remodelling, a physiological process, vital for maintenance of healthy bone tissue in adult humans. In this process, a new bone is formed by osteoblasts and the pre‐existing bone matrix is resorbed by osteoclasts. Imperatorin, a widely available and inexpensive plant extract with antioxidative and apoptotic effects, is reported to treat osteoporosis. However, the underlying mechanism and specific effects on bone metabolism have not been elucidated. In this study, we used rat bone marrow‐derived mesenchymal stem cells and found that imperatorin can activate RUNX2, COL1A1 and osteocalcin by promoting the Ser9 phosphorylation of GSK3β and entry of β‐catenin into the nucleus. Imperatorin also enhanced the production of phospho‐AKT (Ser473), an upstream factor that promotes the Ser9 phosphorylation of GSK3β. We used ipatasertib, a pan‐AKT inhibitor, to inhibit the osteogenic effect of imperatorin, and found that imperatorin promotes osteogenesisviaAKT/GSK3β/β‐catenin pathway. Next, we used rat bone marrow‐derived monocytes, to check whether imperatorin inhibits osteoclast differentiationviaAKT/GSK3β/β‐catenin pathway. Further, we removed the bilateral ovaries of rats to establish an osteoporotic model. Intragastric administration of imperatorin promoted osteogenesis and inhibited osteoclast in vivo. Our experiments showed that imperatorin is a potential drug for osteoporosis treatment.