Dataset Information

Analysis of circulating microRNAs aberrantly expressed in alcohol-induced osteonecrosis of femoral head.

ABSTRACT: Serum miRNAs are potential biomarkers for predicting the progress of bone diseases, but little is known about miRNAs in alcohol-induced osteonecrosis of femoral head (AIONFH). This study evaluated disease-prevention value of specific serum miRNA expression profiles in AIONFH. MiRNA PCR Panel was taken to explore specific miRNAs in serum of AIONFH cases. The top differentially miRNAs were further validated by RT-qPCR assay in serum and bone tissues of two independent cohorts. Their biofunction and target genes were predicted by bioinformatics databases. Target genes related with angiogenesis and osteogenesis were quantified by RT-qPCR in necrotic bone tissue. Our findings demonstrated that multiple miRNAs were evaluated to be differentially expressed with high dignostic values. MiR-127-3p, miR-628-3p, and miR-1 were downregulated, whereas miR-885-5p, miR-483-3p, and miR-483-5p were upregulated in serum and bone samples from the AIONFH patients compared to those from the normal control individuals (p?

SUBMITTER: Hong G

PROVIDER: S-EPMC6908598 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Analysis of circulating microRNAs aberrantly expressed in alcohol-induced osteonecrosis of femoral head.

Hong Guoju G Han Xiaorui X He Wei W Xu Jiake J Sun Ping P Shen Yingshan Y Wei Qiushi Q Chen Zhenqiu Z

Scientific reports 20191212 1

Serum miRNAs are potential biomarkers for predicting the progress of bone diseases, but little is known about miRNAs in alcohol-induced osteonecrosis of femoral head (AIONFH). This study evaluated disease-prevention value of specific serum miRNA expression profiles in AIONFH. MiRNA PCR Panel was taken to explore specific miRNAs in serum of AIONFH cases. The top differentially miRNAs were further validated by RT-qPCR assay in serum and bone tissues of two independent cohorts. Their biofunction an ...[more]

PMID: 31831773

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Project description:The present study aimed to detect the correlations between altered cellular functions in bone marrow stem cells (BMSCs) and osteonecrosis of the femoral head (ONFH). By profiling the aberrant expression of miRNAs and circRNAs in BMSCs isolated from ONFH patients, the present study aimed to further explore the potential regulatory mechanisms of action of circRNAs in ONFH using integrated bioinformatics analysis. BMSCs were isolated from seven ONFH patients and seven controls. Cellular functions, including proliferation, apoptosis and differentiation, were compared. miRNA and circRNA sequencing were conducted using RNA samples of three ONFH patients and three controls to identify differentially expressed circRNAs and miRNAs. The expression of hsa_circ_0000219, hsa_circ_0004588 and hsa_circ_0005936 were validated by qPCR. Target miRNAs were also predicted and validated by qPCR and circRNA‑miRNA co‑expression networks were constructed. BMSCs of ONFH patients displayed decreased proliferation and increased apoptosis during in vitro culturing. In addition, reduced osteogenesis and enhanced adipogenesis were found in the ONFH group. A total of 129 miRNAs and 231 circRNAs were detected to be differentially expressed. The expression levels of hsa_circ_0000219, hsa_circ_0004588 and hsa_circ_0005936 were significantly decreased in BMSCs of ONFH patients. A number of target miRNAs related to cell proliferation, apoptosis and differentiation were predicted for hsa_circ_0000219 and hsa_circ_0005936. The expression levels of miR‑144‑3p and miR‑1270 were found to be elevated in ONFH patients, which was consistent with miRNA sequencing data and competitive endogenous RNA hypothesis. Time‑dependent expression patterns of hsa_circ_0000219, hsa_circ_0004588, hsa_circ_0005936, miR‑144‑3p and miR‑1270 were also validated during osteogenic and adipogenic differentiation in BMSCs. The results of the present study substantiated the involvement of BMSCs in ONFH development. hsa_circ_0000219 and hsa_circ_0005936 may regulate the progression of ONFH by mediating the proliferation and differentiation of BMSCs by sponging miRNAs.

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

Analysis of circulating microRNAs aberrantly expressed in alcohol-induced osteonecrosis of femoral head.

Publications

Analysis of circulating microRNAs aberrantly expressed in alcohol-induced osteonecrosis of femoral head.

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