title: Experimental rat model for alcohol-induced osteonecrosis of the femoral head.
abstract: Alcohol-induced osteonecrosis of the femoral head (ONFH) is observed in alcohol abusers and patients with alcoholic fatty liver disease. It has been reported that Toll-like receptor 4 (TLR4) signalling plays a crucial role in the pathogenesis of alcoholic fatty liver disease. We previously reported a corticosteroid-induced ONFH rat model, and suggested that TLR4 signalling contributes to the pathogenesis of ONFH. Thus, it is thought that the pathogenesis of alcohol-induced ONFH is probably similar to that of corticosteroid-induced ONFH. The aim of this study was to develop a new animal model for alcohol-induced ONFH and to evaluate the relationship between the pro-inflammatory response via TLRs and the development of ONFH in rats. Male Wistar rats were fed a Lieber-DeCarli liquid diet containing 5% ethanol (experimental group) or dextran (control group) for 1-24 weeks. Histopathological and biochemical analyses were performed. Feeding the ethanol-containing liquid diet resulted in the development of ONFH with hepatic steatosis, hepatic dysfunction and hyperlipidaemia, whereas feeding the dextran-containing diet did not cause ONFH. However, we could not recognize any relationship between the pro-inflammatory response via TLR4 and the development of alcohol-induced ONFH. Thus in this study we have developed a new rat model for alcohol-induced ONFH based on the feeding of an ethanol liquid diet. ONFH was observed within seven days from the start of feeding with 5% ethanol-containing liquid diet. Although this was linked to hepatic steatosis, a TLR4 association was not a feature of this model.
authors.affiliation: Department of Musculoskeletal Biomechanics and Surgical Development, School of Medicine, Sapporo Medical University, Sapporo, Japan; Department of Legal Medicine and Molecular Alcohology, School of Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Shunichiro
authors.initials: S
authors.lastname: Okazaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nagoya
authors.forename: Kenji
authors.initials: K
authors.lastname: Tateda
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Katada
authors.forename: Keisuke
authors.initials: K
authors.lastname: Mizuo
authors.forename: Satoshi
authors.initials: S
authors.lastname: Watanabe
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yamashita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D000431:Ethanol / Q000009:adverse effects*; D005271:Femur Head Necrosis / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D010020:Osteonecrosis / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000502:physiology
chemical_list: C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D000431:Ethanol
keywords: alcohol; animal model; femoral head osteonecrosis; toll-like receptor
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