Abstract 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 partly via PI3K/AKT pathway and retard the promotion of alcohol‐induced adipogenesis via AMPK 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 possibly via regulating the differentiation tendency of BMSCs. Hence, CPA may become a beneficial herb extract to alleviate alcohol‐induced ONFH.

中文翻译：

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大黄酸改变骨髓间充质干细胞的分化趋势以预防酒精性股骨头坏死

摘要 目的股骨头坏死（ONFH）主要由酗酒引起，是一种难治性骨病，其特征是骨间充质干细胞（BMSCs）成骨分化能力受损，脂肪细胞堆积紊乱。Chrysophanic acid (CPA) 是一种天然蒽醌，具有调节脂质和骨骼保护能力。本研究的目的是揭示 CPA 的潜在功能和酒精诱导 ONFH 的潜在机制。材料和方法 通过细胞增殖、诱导分化试验和免疫荧光染色研究酒精和 CPA 对 BMSCs 的影响。同时，分别研究了PI3K/AKT和AMPK通路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，以使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 可以部分通过 PI3K/AKT 途径抵消酒精的抗成骨作用，并通过 AMPK 途径阻止酒精诱导的脂肪生成。在体内，放射学和组织病理学发现表明，CPA 可以减轻酒精诱导的 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 可能成为一种有益的草药提取物，以减轻酒精引起的 ONFH。