Chrysophanic acid shifts the differentiation tendency of BMSCs to prevent alcohol-induced osteonecrosis of the femoral head
Chrysophanic acid shifts the differentiation tendency of BMSCs to prevent alcohol-induced osteonecrosis of the femoral head
复制标题
大黄酸改变BMSCs分化倾向预防酒精性股骨头坏死
DOI：
10.1111/cpr.12871
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发表时间：
2020-06-29
影响因子：
8.5
通讯作者：
Gao, Youshui
中科院分区：
文献类型：
--
作者：
Yu, Hongping;Liu, Pei;Gao, Youshui
目的 股骨头坏死（ONFH）是一种难治性骨病，主要由酗酒引起，其特征是骨髓间充质干细胞（BMSC）成骨分化能力受损以及脂肪细胞堆积紊乱。大黄酸（CPA）是一种天然蒽醌，具有调节血脂和保护骨骼的能力。本研究的目的是揭示 CPA 的潜在功能以及酒精诱发 ONFH 的潜在机制。材料和方法通过细胞增殖、诱导分化测定和免疫荧光染色研究酒精和CPA对BMSC的影响。同时，研究了PI3K/AKT和AMPK通路分别在成骨和成脂分化过程中的功能。此外，我们建立了酒精诱导的 ONFH 大鼠模型，利用放射学和组织病理学方法揭示 CPA 的体内药物治疗作用。结果在体外，酒精显着抑制BMSCs的增殖和成骨分化，但刺激成脂分化。然而，CPA可以通过PI3K/AKT途径部分抵消酒精的抗成骨作用，并通过AMPK途径延缓酒精诱导的脂肪生成。在体内，放射学和组织病理学结果表明，CPA 可以减轻酒精引起的 ONFH 并显着恢复骨量。结论我们证明CPA可能通过调节BMSCs的分化趋势来改善酒精诱导的ONFH。因此，CPA 可能成为缓解酒精引起的 ONFH 的有益草药提取物。
Objectives Osteonecrosis of the femoral head (ONFH), largely caused by alcohol abuse, is a refractory bone disease characterized by the impaired capacity of osteogenic differentiation of bone mesenchymal stem cells (BMSCs), as well as the disordered adipocyte accumulation. Chrysophanic acid (CPA) is a natural anthraquinone which has lipid regulation and bone protection capacity. The aim of this study was to reveal the potential function of CPA and the underlying mechanisms for the alcohol-induced ONFH. Materials and Methods The effects of alcohol and CPA on BMSCs were investigated by cell proliferation, induced differentiation assays and immunofluorescent staining. Meanwhile, the function of PI3K/AKT and AMPK pathway was investigated in the process of osteogenic and adipogenic differentiation, respectively. Furthermore, we established the rat model of alcohol-induced ONFH to reveal the pharmacotherapeutic effect of CPA in vivo using radiographical and histopathological methods. Results In vitro, alcohol significantly inhibited the proliferation and osteogenic differentiation of BMSCs but stimulated the adipogenic differentiation. However, CPA could counteract the anti-osteogenesis of alcohol partlyviaPI3K/AKT pathway and retard the promotion of alcohol-induced adipogenesisviaAMPK pathway. In vivo, radiographical and histopathological findings showed that CPA could alleviate alcohol-induced ONFH and substantially restore the bone volume. Conclusions We demonstrated that CPA ameliorated alcohol-induced ONFH possiblyviaregulating the differentiation tendency of BMSCs. Hence, CPA may become a beneficial herb extract to alleviate alcohol-induced ONFH.