Abstract
BackgroundFemoral 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.MethodsMale 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.ResultsFemoral 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.ConclusionsCorticosteroids 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.
Highlights
Femoral head osteonecrosis is frequently observed in patients treated with excessive corticosteroids
There were significant differences between group A and B (p < 0.05). These results suggested that the glucocorticoids could make the osteoclasts activate and the Toll-like receptor 4 (TLR4) antagonists could reduce the activation of osteoclasts
These results showed that the model of steroid-induced femoral head osteonecrosis had been successfully established
Summary
Femoral head osteonecrosis is frequently observed in patients treated with excessive corticosteroids. Steroid-induced osteonecrosis of femoral head often leads to progressive collapse and followed by degenerative arthritis It is frequently caused by excessive corticosteroids administration. To examine the pathogenesis of steroid-induced osteonecrosis, a disseminated intravascular coagulation shock rabbit model has been developed in which osteonecrosis is induced by administering lipopolysaccharide (LPS) and methylprednisolone (MP) [11] This model shows metaphysic osteonecrosis and not the epiphysic necrosis that is observed in human patients. To overcome these limitations, a rat model has been developed in which osteonecrosis is induced by excessive MP [12,13,14]. The femoral anteversion and neck-shaft angle of rats are similar to that of humans, and the mechanical property of the structures can be similar
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
