Open Access Open Badges Research article

Immune response associated with Toll-like receptor 4 signaling pathway leads to steroid-induced femoral head osteonecrosis

Lei Tian12, Qi Wen3, Xiaoqian Dang1, Wulin You1, Lihong Fan1 and Kunzheng Wang1*

Author Affiliations

1 Department of Orthopedics Surgery, The Second Affiliated Hospital, College of Medicine, Xi’an Jiaotong University Xi’an, Xi’an, Shaanxi 710061, PR China

2 Department of Orthopedics Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, PR China

3 Department of Orthopedics Surgery, the Second People’s Hospital of Shaanxi Province, Xi’an, Shaanxi 710061, PR China

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BMC Musculoskeletal Disorders 2014, 15:18  doi:10.1186/1471-2474-15-18

Published: 15 January 2014



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.


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.


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.


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.

Osteonecrosis; Femoral head; Toll-like receptor 4; Corticosteroids; Rat