Dataset Information

Activation of aldehyde dehydrogenase 2 protects ethanol-induced osteonecrosis of the femoral head in rat model.

ABSTRACT:

Objectives

Osteonecrosis of the femoral head (ONFH) is a devastating disease characterized by destructive bone structures, enlarged adipocyte accumulation and impaired vascularization. The aldehyde dehydrogenase 2 (ALDH 2) is the limiting enzyme for ethanol metabolism with many physiological functions. The aim was investigated the potential protective role of activated ALDH 2 by Alda-1 for ethanol-induced ONFH.

Materials and methods

The ethanol-induced ONFH in rat was performed to explore the protective of Alda-1 by various experimental methods. Subsequently, the effect of Alda-1 and ethanol on the osteogenic and adipogenic differentiation was investigated via multiple cellular and molecular methods. Finally, the effect of Alda-1 and ethanol on the neo-vascularization was detected in Human umbilical vein endothelial cells (HUVECs) and ONFH model.

Results

Firstly, radiographical and pathological measurements indicated that alda-1 protected ethanol-induced ONFH. Moreover, ethanol significantly inhibited the proliferation and osteogenic differentiation of BMSCs, whereas Alda-1 could distinctly rescue it by PI3K/AKT signalling. Secondly, ethanol remarkably promoted the lipid vacuoles formation of BMSCs, while Alda-1 significantly retarded it on BMSCs by AMPK signalling pathway. Finally, ethanol significantly inhibited proliferation and growth factor level resulting in reduced angiogenesis, whereas Alda-1 could rescue the effect of ethanol. Additionally, Alda-1 significantly reduced the occurrence of ONFH and promoted vessel number and distribution in alcoholic ONFH.

Conclusions

Alda-1 activation of ALDH 2 was highly demonstrated to protect ethanol-induced ONFH by triggering new bone formation, reducing adipogenesis and stimulating vascularization.

SUBMITTER: Lin X

PROVIDER: S-EPMC9201375 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

Activation of aldehyde dehydrogenase 2 protects ethanol-induced osteonecrosis of the femoral head in rat model.

Lin Xiaoyi X Zhu Daoming D Wang Kaiyang K Luo Pengbo P Rui Gang G Gao Youshui Y Liu Fuan F Yu Hongping H

Cell proliferation 20220514 6

<h4>Objectives</h4>Osteonecrosis of the femoral head (ONFH) is a devastating disease characterized by destructive bone structures, enlarged adipocyte accumulation and impaired vascularization. The aldehyde dehydrogenase 2 (ALDH 2) is the limiting enzyme for ethanol metabolism with many physiological functions. The aim was investigated the potential protective role of activated ALDH 2 by Alda-1 for ethanol-induced ONFH.<h4>Materials and methods</h4>The ethanol-induced ONFH in rat was performed to ...[more]

PMID: 35567426

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Project description:BackgroundThe absolute number of femoral neck fractures (FNFs) is increasing; however, the prediction of traumatic femoral head necrosis remains difficult. Machine learning algorithms have the potential to be superior to traditional prediction methods for the prediction of traumatic femoral head necrosis.ObjectiveThe aim of this study is to use machine learning to construct a model for the analysis of risk factors and prediction of osteonecrosis of the femoral head (ONFH) in patients with FNF after internal fixation.MethodsWe retrospectively collected preoperative, intraoperative, and postoperative clinical data of patients with FNF in 4 hospitals in Shanghai and followed up the patients for more than 2.5 years. A total of 259 patients with 43 variables were included in the study. The data were randomly divided into a training set (181/259, 69.8%) and a validation set (78/259, 30.1%). External data (n=376) were obtained from a retrospective cohort study of patients with FNF in 3 other hospitals. Least absolute shrinkage and selection operator regression and the support vector machine algorithm were used for variable selection. Logistic regression, random forest, support vector machine, and eXtreme Gradient Boosting (XGBoost) were used to develop the model on the training set. The validation set was used to tune the model hyperparameters to determine the final prediction model, and the external data were used to compare and evaluate the model performance. We compared the accuracy, discrimination, and calibration of the models to identify the best machine learning algorithm for predicting ONFH. Shapley additive explanations and local interpretable model-agnostic explanations were used to determine the interpretability of the black box model.ResultsA total of 11 variables were selected for the models. The XGBoost model performed best on the validation set and external data. The accuracy, sensitivity, and area under the receiver operating characteristic curve of the model on the validation set were 0.987, 0.929, and 0.992, respectively. The accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve of the model on the external data were 0.907, 0.807, 0.935, and 0.933, respectively, and the log-loss was 0.279. The calibration curve demonstrated good agreement between the predicted probability and actual risk. The interpretability of the features and individual predictions were realized using the Shapley additive explanations and local interpretable model-agnostic explanations algorithms. In addition, the XGBoost model was translated into a self-made web-based risk calculator to estimate an individual's probability of ONFH.ConclusionsMachine learning performs well in predicting ONFH after internal fixation of FNF. The 6-variable XGBoost model predicted the risk of ONFH well and had good generalization ability on the external data, which can be used for the clinical prediction of ONFH after internal fixation of FNF.

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

Activation of aldehyde dehydrogenase 2 protects ethanol-induced osteonecrosis of the femoral head in rat model.

Objectives

Materials and methods

Results

Conclusions

Publications

Activation of aldehyde dehydrogenase 2 protects ethanol-induced osteonecrosis of the femoral head in rat model.

Similar Datasets

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