单纯激素-Immune response associated with Toll-like receptor 4 signaling pathway leads to steroid-induced femoral head osteonecrosis.pdfVIP

Tian et al. BMC Musculoskeletal Disorders 2014, 15:18 /1471-2474/15/18 RESEARCH ARTICLE Open Access Immune response associated with Toll-like receptor 4 signaling pathway leads to steroid-induced femoral head osteonecrosis 1,2 3 1 1 1 1* Lei Tian , Qi Wen , Xiaoqian Dang , Wulin You , Lihong Fan and Kunzheng Wang 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