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The defensive effect of nitric oxide on the pathogenesis of steroid‐induced femoral head osteonecrosis
Author(s) -
Kenji Tateda,
Okazaki Shunichiro,
Watanebe Satoshi,
Katada Ryuichi,
Mizuo Keisuke,
Nagoya Satoshi,
Yamashita Toshihiko,
Matsumoto Hiroshi
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb431
Subject(s) - pathogenesis , lipopolysaccharide , nitric oxide , femoral head , medicine , endocrinology , nitric oxide synthase , group b , group a , chemistry , immunology , surgery
Objectives Femoral head osteonecrosis(ON) is observed in patients treated with steroids. However, the pathogenesis of ON remains unclear. Nitic oxide(NO) is known to be related to the pathogenesis of osteonecrosis. Last year we established a rat model with ON by injecting lipopolysaccharide(LPS) and MP, and this was associated with a disruption of the innate immune system. In the present study, we investigated the effects of NO on pathogenesis of ON in our rat model. Methods Male Wistar rats were injected intravenously with 2mg/kg LPS on days 0 and 1 and intramascularly with 20mg/kg MP on days 2, 3 and 4, and then intraperitoneally with 50mg/kg NG‐nitro‐L‐arginine methyl ester(L‐NAME), an NO synthase inhibitor, on days 5,6 and 7 in group A, and on days 11,12 and 13 in group B. The animals were sacrificed 2 weeks after the last MP injection. Blood cytokines and other factors were performed by multiplex analysis system using Luminex. Results ON was observed in 67% of group A, not observed in group B. The plasma AST and ALT concentrations were increased in group A and B. The plasma IFN‐gamma concentrations were significantly higher in group A and B compared with control. The plasma IL‐17 concentrations were significantly higher in group B than control, while IL‐17 levels in group A were not different from those in control. Conclusions Inhibition of NO production just after MP injection caused ON in the rat model. IL‐17 levels were decreased in the rats with ON indicating that NO and IL‐17 may have defensive effects on pathogenesis of ON.