title: Immune response associated with Toll-like receptor 4 signaling pathway leads to steroid-induced femoral head osteonecrosis.
abstract: BACKGROUND
  Femoral head osteonecrosis is frequently observed in patients treated with excessive corticosteroids. The objective of the current study was to establish a rat model to investigate the disruption of immune response in steroid-induced femoral head osteonecrosis via Toll-like receptor 4 (TLR4) signaling pathway.
  
  
  METHODS
  Male SD rats were divided into the treatment group (group A) and the model group (group B) consisting of 24 rats each, and were injected intramuscularly with 20 mg/kg methylprednisolone (MP) for 8 weeks, once a week. The rats in group A were injected intravenously with 7.5 mg/kg TAK242 before each MP administration. A control group (group N) consisted of 12 rats were received saline injection. All animals were sacrificed 8, 10 and 12 weeks from the first MP injection, respectively. Histopathological analysis was performed and the concentration of tartrate-resistant acid phosphatase (TRAP) in serum was tested. The signaling molecules including TLR4, MyD88, NF-κB p65 and MCP-1 were detected by immunohistochemistry, quantitative real-time PCR and Western blot.
  
  
  RESULTS
  Femoral head osteonecrosis was observed in the model rats, and the concentration of TRAP and positive staining of all signaling molecules increased significantly in group B compared with that in group A and group N. Compare with the control group, the mRNA expressions and protein levels of all signaling molecules were enhanced significantly in group B, but no significant in group A.
  
  
  CONCLUSIONS
  Corticosteroids can induce femoral head osteonecrosis by disturbing the immune response via TLR4 signaling pathway. These findings suggest that the disruption of immune response play a role in the pathogenesis of osteonecrosis.
authors.forename: Lei
authors.initials: L
authors.lastname: Tian
authors.forename: Qi
authors.initials: Q
authors.lastname: Wen
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Dang
authors.forename: Wulin
authors.initials: W
authors.lastname: You
authors.forename: Lihong
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Orthopedics Surgery, The Second Affiliated Hospital, College of Medicine, Xi'an Jiaotong University Xi'an, Xi'an, Shaanxi 710061, PR China. wkzh1955@gmail.com.
authors.forename: Kunzheng
authors.initials: K
authors.lastname: Wang
mesh_terms: D000135:Acid Phosphatase / Q000097:blood; D000305:Adrenal Cortex Hormones; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005271:Femur Head Necrosis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007527:Isoenzymes / Q000097:blood; D008297:Male; D008775:Methylprednisolone; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D000071681:Tartrate-Resistant Acid Phosphatase; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism
chemical_list: D000305:Adrenal Cortex Hormones; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D007527:Isoenzymes; C507781:Myd88 protein, rat; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; C498145:Rela protein, rat; D013449:Sulfonamides; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; C507035:ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D008775:Methylprednisolone