title: Femoral head osteonecrosis can be caused by disruption of the systemic immune response via the toll-like receptor 4 signalling pathway.
abstract: OBJECTIVE
  Osteonecrosis of the femoral head is observed in patients treated with steroids. However, the pathogenesis of femoral head osteonecrosis remains unclear. We established a rat model with femoral head osteonecrosis by injecting lipopolysaccharide (LPS) and steroid, and assessed the consequences of this on femoral head histology, the systemic immune response and lipid synthesis.
  
  
  METHODS
  Male Wistar rats were injected intravenously on days 0 and 1 with 2 mg/kg LPS and intramuscularly with 20 mg/kg methylprednisolone on days 3, 4 and 5. The animals were sacrificed 1, 2, 3 or 4 weeks after the last methylprednisolone injection. Histopathological and biochemical analyses were performed every week.
  
  
  RESULTS
  Osteonecrosis of the femoral head was observed in the rats. The plasma triglyceride concentrations had decreased significantly by weeks 2 and 3. The total plasma cholesterol concentrations had increased significantly by week 1 but then decreased significantly by week 4. The plasma concentrations of IL-1beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma and TNF-alpha had increased significantly by week 1. These cytokines can all be induced by toll-like receptor 4 (TLR4) signalling.
  
  
  CONCLUSIONS
  LPS and methylprednisolone induced osteonecrosis of the femoral head in rats and this was associated with a disruption of the innate immune system and lipid synthesis. These findings suggest that the TLR4 signalling pathway plays an important role in the pathogenesis of femoral head osteonecrosis.
authors.affiliation: Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Okazaki
authors.forename: Y
authors.initials: Y
authors.lastname: Nishitani
authors.forename: S
authors.initials: S
authors.lastname: Nagoya
authors.forename: M
authors.initials: M
authors.lastname: Kaya
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
authors.forename: H
authors.initials: H
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D005271:Femur Head Necrosis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D005786:Gene Expression Regulation / Q000276:immunology; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D008297:Male; D008775:Methylprednisolone; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D014280:Triglycerides / Q000097:blood
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D014280:Triglycerides; D002784:Cholesterol; D008775:Methylprednisolone