Open AccessOsthole stimulates bone formation, drives vascularization and retards adipogenesis to alleviate alcohol‐induced osteonecrosis of the femoral head
Author(s) -
Yu Hongping,
Zhu Daoyu,
Liu Pei,
Yang Qianhao,
Gao Junjie,
Huang Yigang,
Chen Yixuan,
Gao Youshui,
Zhang Changqing
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.15103
Subject(s) - adipogenesis , mesenchymal stem cell , vasculogenesis , chemistry , wnt signaling pathway , oil red o , in vivo , human umbilical vein endothelial cell , umbilical vein , medicine , microbiology and biotechnology , pathology , endothelial stem cell , in vitro , biology , signal transduction , biochemistry
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.