Osthole stimulates bone formation, drives vascularization and retards adipogenesis to alleviate alcohol-induced osteonecrosis of the femoral head
Osthole stimulates bone formation, drives vascularization and retards adipogenesis to alleviate alcohol-induced osteonecrosis of the femoral head
复制标题
蛇床子素刺激骨形成，促进血管化并延缓脂肪生成，以减轻酒精引起的股骨头坏死
DOI：
10.1111/jcmm.15103
复制
发表时间：
2020-04-01
影响因子：
5.3
通讯作者：
Zhang, Changqing
中科院分区：
文献类型：
--
作者：
Yu, Hongping;Zhu, Daoyu;Zhang, Changqing
股骨头坏死(ONFH)的典型病理改变包括骨髓间充质干细胞(BMSCs)成骨分化减少、骨循环障碍和髓内脂肪细胞沉积增加。蛇床子素是香豆素的生物活性衍生物，具有广泛的药物治疗作用。本研究旨在揭示蛇床子素对酒精性股骨头坏死的潜在保护作用。在体外，乙醇(50 mm o l/L)显著抑制骨髓间充质干细胞的增殖和成骨分化，抑制人脐静脉内皮细胞的增殖和成管能力，但显著促进骨髓间充质干细胞的成脂分化。蛇床子素通过调节Wnt/β-catenin通路，刺激血管生成，抑制脂肪生成，从而逆转乙醇对成骨的影响。在体内，蛇床子素的保护作用在构建良好的乙醇诱导的ONFH大鼠模型中得到证实，一系列的放射和病理检查包括显微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这一作用。综上所述，蛇床子素首次被证明通过促进骨形成、推动血管形成和抑制脂肪生成来挽救乙醇诱导的ONFH。
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/beta-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.