Inhibiton of IRF7 prevents developing corticosteroid‐induced osteonecrosis of the femoral head

Abstract

ObjectivesWe 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.MethodsMale 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.ResultsThe 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.ConclusionsThe present study shows that inhibition of IRF7 activity by the kinase inhibitor prevents ONFH.