Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
J Cell Mol Med. 2020 Apr;24(8):4439-4451. doi: 10.1111/jcmm.15103. Epub 2020 Mar 5.
Characteristic pathological changes in osteonecrosis of the femoral head (ONFH) include reduced osteogenic differentiation of bone mesenchymal stem cells (BMSCs), impaired osseous circulation and increased intramedullary adipocytes deposition. Osthole is a bioactive derivative from coumarin with a wide range of pharmacotherapeutic effects. The aim of this study was to unveil the potential protective role of osthole in alcohol-induced ONFH. In vitro, ethanol (50 mmol/L) remarkably decreased the proliferation and osteogenic differentiation of BMSCs and impaired the proliferation and tube formation capacity of human umbilical vein endothelial cell (HUVECs), whereas it substantially promoted the adipogenic differentiation of BMSCs. However, osthole could reverse the effects of ethanol on osteogenesis via modulating Wnt/β-catenin pathway, stimulate vasculogenesis and counteract adipogenesis. In vivo, the protective role of osthole was confirmed in the well-constructed rat model of ethanol-induced ONFH, demonstrated by a cascade of radiographical and pathological investigations including micro-CT scanning, haematoxylin-eosin staining, TdT-mediated dUTP nick end labelling, immunohistochemical staining and fluorochrome labelling. Taken together, for the first time, osthole was demonstrated to rescue the ethanol-induced ONFH via promoting bone formation, driving vascularization and retarding adipogenesis.
股骨头坏死（ONFH）的特征性病理变化包括成骨细胞分化减少、骨内血液循环受损和骨髓内脂肪细胞沉积增加。蛇床子素是香豆素的一种生物活性衍生物，具有广泛的治疗作用。本研究旨在揭示蛇床子素在酒精诱导的 ONFH 中的潜在保护作用。体外实验结果表明，乙醇（50mmol/L）显著降低了骨髓间充质干细胞的增殖和成骨分化能力，并损害了人脐静脉内皮细胞（HUVECs）的增殖和管腔形成能力，而明显促进了骨髓间充质干细胞的成脂分化。然而，蛇床子素可以通过调节 Wnt/β-catenin 通路来逆转乙醇对成骨的影响，刺激血管生成并拮抗成脂分化。在体内，通过一系列影像学和病理学研究，包括 micro-CT 扫描、苏木精-伊红染色、TdT 介导的 dUTP 缺口末端标记、免疫组织化学染色和荧光标记，证实了蛇床子素在乙醇诱导的大鼠 ONFH 模型中具有保护作用。综上所述，首次证明蛇床子素通过促进骨形成、促进血管生成和抑制脂肪生成来挽救乙醇诱导的 ONFH。
