MyD88‐independent pathway plays an important role in alcohol‐induced osteonecrosis

Abstract

ObjectivesOsteonecrosis of the femoral head (ONF) occurs under steroid therapy or chronic alcohol consumption. Most of patients with alcohol‐induced ONF contract alcoholic fatty liver disease, in the pathogenesis of which LPS, a ligand of TLR4, plays a crucial role. However, the pathogenesis of alcohol‐induced ONF remains unclear. In the present study, we found that feeding alcohol liquid diet for experimental alcoholic fatty liver disease causes ONF and clarified role of proinflammatory responses in the pathogenesis.MethodsMale Wistar rats were fed Lieber DeCarli liquid diet containing 5% ethanol or dextran for 1–6 weeks. Histopathological and biochemical analyses were performed.ResultsAlcohol liquid diet feeding remarkably promoted ONF. The animal had hepatic steatosis, liver dysfunction, and hyperlipidemia as well as many previous reports. Blood IFN gamma was increased in the rat fed with alcohol liquid diet, while adiponectin levels was decreased in the rat. IFN gamma and adiponectin can be related to TLR4 understream pathways via MyD88‐independent and dependent.ConclusionsWe found ONF in the rat fed alcohol liquid diet. The animal showed elevated IFN gamma and decreased adiponectin, suggesting that IFN gamma signaling pathway may play a crucial role in the pathogenesis of alcohol‐induced osteonecrosis of the femoral head.