title: Huogu I formula prevents steroid-induced osteonecrosis in rats by down-regulating PPARgamma expression and activating wnt/LRP5/ beta-catenin signaling.
abstract: OBJECTIVE
  To investigate the effects of Huogu I formula on regulation of lipid metabolism in steroid-induced osteonecrosis of the femoral head (SONFH) rats and verify our hypothesis that Huogu I formula regulates lipid metabolism by down-regulating peroxisome proliferator-activated receptor gamma (PPARgamma) expression and activating Wnt signaling pathways.
  
  
  METHODS
  Eighty-five rats were divided into four groups: control, model, Huogu 15 g/kg and Huogu 30 g/kg. Six weeks later, animals were anaesthetized, femora was dissected for histopathological examination of the osteonecrotic changes and repair processes, micro computed tomography (Micro-CT)-based micro-angiography was performed to assess vascularization. Serum lipid levels were detected by haematological examination. The expressions of PPARy, Wnt3a, low density lipoprotein receptor-related protein 5 (LRP5) and beta-catenin were evaluated by immunohistochemistry, Western blot and quantitative real-time polymerase chain reaction analyses.
  
  
  RESULTS
  The incidence of osteonecrosis, ratio of empty lacuna, adipose tissue area and adipocyte perimeter in the bone marrow were dramatically lower in the Huogu I formula treatment groups. By micro-CT quantification, Huogu I formula treatment dose-dependently increased vessel volume, vessel surface, percentage of vessel volume and vessel thickness of the femoral heads of SONFH rats. Levels of serum lipid in Huogu 15 g/kg and Huogu 30 g/kg groups reduced significantly. Huogu I formula treatment could suppress the expression of PPARy and increase the expressions of Wnt3a, LRP5 and beta-catenin at both protein and mRNA levels.
  
  
  CONCLUSIONS
  The results of our present study highlight the lipid-lowering potential of Huogu I formula, and provide further evidence of the involvement of the PPARgamma inhibition and Wnt/LRP5/ beta-catenin signaling activation in the effects of Huogu I formula.
authors.forename: Yini
authors.initials: Y
authors.lastname: Jiang
authors.forename: Daobing
authors.initials: D
authors.lastname: Liu
authors.forename: Xiangying
authors.initials: X
authors.lastname: Kong
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Weiheng
authors.initials: W
authors.lastname: Chen
authors.forename: Na
authors.initials: N
authors.lastname: Lin
mesh_terms: D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D006801:Humans; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D010020:Osteonecrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013256:Steroids / Q000009:adverse effects*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D004365:Drugs, Chinese Herbal; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D047495:PPAR gamma; D013256:Steroids; D051153:Wnt Proteins; D051176:beta Catenin