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Inhibiton of IRF7 prevents developing corticosteroid‐induced osteonecrosis of the femoral head
Author(s) -
OKAZAKI Shunichiro,
NAGOYA Satoshi,
KATADA Ryuichi,
MIZUO Keisuke,
SASAKI Mikito,
WATANABE Satoshi,
YAMASHITA Toshihiko,
MATSUMOTO Hiroshi
Publication year - 2013
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.27.1_supplement.874.7
Subject(s) - femoral head , medicine , pharmacology , methylprednisolone , kinase , corticosteroid , irf7 , avascular necrosis , chemistry , surgery , receptor , biochemistry , innate immune system
Objectives We previously reported that corticosteroid induced osteonecrosis of the femoral head (ONFH) occurs under activation of NF‐ƒÈB and IRF7 by TLR ligand administration, followed by reduction of NF‐ƒÈB activation after corticosteroid treatment. In the present study, we proved that the reduction of IRF7 activity by an IkB kinase inhibitor prevents ONFH. Methods Male Wistar rats (n=66) were randomly divided into two groups. Each group rats were given ligands of TLR7 on day 1 and methylprednisolone with or without an IkB kinase inhibitor on day 2. Animals were sacrificed 1 or 14 days after last injection. Histopathological and biochemical analyses were then performed. Results The incidence of ONFH was decreased dose dependently by the IkB kinase inhibitor. The activity of IRF7 was significantly decreased after IkB kinase inhibitor administration, but the activity of NF‐kB did not changed. Conclusions The present study shows that inhibition of IRF7 activity by the kinase inhibitor prevents ONFH.