Dataset Information

The protective effect of PFT? on alcohol-induced osteonecrosis of the femoral head.

ABSTRACT: Epidemiologic studies have shown alcohol plays a pivotal role in the development of osteonecrosis of the femoral head (ONFH). The aim of this study was to explore the underlying mechanism of alcohol-induced ONFH and the protective effect of pifithrin-? (PFT?). In vitro, we found ethanol treatment significantly activated p53, suppressed Wnt/?-catenin signaling and inhibited osteogenic-related proteins. Furthermore, by separating the cytoplasmic and nuclear proteins, we found ethanol inhibited osteogenesis by impairing the accumulation of ?-catenin in both the cytoplasm and nucleus in human bone mesenchymal stem cells (hBMSCs), which resulted from activating glycogen synthase kinase-3? (GSK-3?). Therefore, PFT?, a p53 inhibitor, was introduced in this study to block the ethanol-triggered activation of p53 in hBMSCs and alcohol-induced ONFH in a rat model. In vivo, we established alcohol-induced ONFH in rats and investigated the protective effect of PFT?. Hematoxylin & eosin (H&E) staining combined with TdT-mediated dUTP nick end labeling (TUNEL), cleaved caspase-3 immunohistochemical staining, and micro-CT images revealed substantial ONFH in the alcohol-administered rats, whereas significantly less osteonecrosis developed in the rats injected with PFT?. Osteogenic-related proteins, including osteocalcin, osteopontin and collagen I, were significantly decreased in the alcohol-administered rats, whereas these results were reversed in the PFT?-injected rats. Fluorochrome labeling similarly showed that alcohol significantly reduced the osteogenic activity in the rat femoral head, which was blocked by the injection of PFT?. In conclusion, PFT? had an antagonistic effect against the effects of ethanol on hBMSCs and could be a clinical strategy to prevent the development of alcohol-induced ONFH.

SUBMITTER: Chen YX

PROVIDER: S-EPMC5725055 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The protective effect of PFTα on alcohol-induced osteonecrosis of the femoral head.

Chen Yi-Xuan YX Zhu Dao-Yu DY Yin Jun-Hui JH Yin Wen-Jing WJ Zhang Yue-Lei YL Ding Hao H Yu Xiao-Wei XW Mei Jiong J Gao You-Shui YS Zhang Chang-Qing CQ

Oncotarget 20170711 59

Epidemiologic studies have shown alcohol plays a pivotal role in the development of osteonecrosis of the femoral head (ONFH). The aim of this study was to explore the underlying mechanism of alcohol-induced ONFH and the protective effect of pifithrin-α (PFTα). In vitro, we found ethanol treatment significantly activated p53, suppressed Wnt/β-catenin signaling and inhibited osteogenic-related proteins. Furthermore, by separating the cytoplasmic and nuclear proteins, we found ethanol inhibited ost ...[more]

PMID: 29246013

Similar Datasets

Project description:BackgroundGlucocorticoid usage and alcohol abuse are the most widely accepted risk factors for nontraumatic osteonecrosis of femoral head (ONFH). Despite distinct etiologies between glucocorticoid-associated ONFH (GONFH) and alcohol-associated ONFH (AONFH), little is known about the differences of the microarchitectural and histomorphologic characteristics between these subtypes of ONFH.PurposesTo investigate bone microarchitecture, bone remodeling activity and histomorphology characteristics of different regions in femoral heads between GONFH and AONFH.MethodsFrom September 2015 to October 2020, 85 patients diagnosed with GONFH and AONFH were recruited. Femoral heads were obtained after total hip replacement. Femoral head specimens were obtained from 42 patients (50 hips) with GONFH and 43 patients (50 hips) with AONFH. Micro-CT was utilized to assess the microstructure of 9 regions of interest (ROIs) in the femoral head. Along the supero-inferior orientation, the femoral head was divided into necrotic region, reactive interface, and normal region; along the medio-lateral orientation, the femoral head was divided into medial region, central region and lateral region. Decalcified and undecalcified bone histology was subsequently performed to evaluate histopathological alterations and bone remodeling levels.ResultsIn the necrotic region, most of the microarchitectural parameters did not differ significantly between GONFH and AONFH, whereas both the reactive interface and normal region revealed a less sclerotic microarchitecture but a higher bone remodeling level in GONFH than AONFH. Despite similar necrotic pathological manifestations, subchondral trabecular microfracture in the necrotic region was more severe and vasculature of the reactive interface was more abundant in GONFH.ConclusionsGONFH and AONFH shared similar microarchitecture and histopathological features in the necrotic region, while GONFH exhibited a less sclerotic microarchitecture and a more active bone metabolic status in both the reactive interface and normal region. These differences between GONFH and AONFH in bone microarchitectural and histopathological characteristics might contribute to the development of disease-modifying prevention strategies and treatments for ONFH, taking into etiologies.

Dataset Information

The protective effect of PFT? on alcohol-induced osteonecrosis of the femoral head.

Publications

The protective effect of PFTα on alcohol-induced osteonecrosis of the femoral head.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets