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Bone-Metabolism-Related Serum microRNAs to Diagnose Osteoporosis in Middle-Aged and Elderly Women

Objective: Postmenopausal osteoporosis (PMOP), a chronic systemic metabolic disease prevalent in middle-aged and elderly women, heavily relies on bone mineral density (BMD) measurement as the diagnostic indicator. In this study, we investigated serum microRNAs (miRNAs) as a possible screening tool f...

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Autores principales: Zhao, Sheng-Li, Wen, Zhen-Xing, Mo, Xiao-Yi, Zhang, Xiao-Yan, Li, Hao-Nan, Cheung, Wing-Hoi, Fu, Dan, Zhang, Shi-Hong, Wan, Yong, Chen, Bai-Ling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9689310/
https://www.ncbi.nlm.nih.gov/pubmed/36428932
http://dx.doi.org/10.3390/diagnostics12112872
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author Zhao, Sheng-Li
Wen, Zhen-Xing
Mo, Xiao-Yi
Zhang, Xiao-Yan
Li, Hao-Nan
Cheung, Wing-Hoi
Fu, Dan
Zhang, Shi-Hong
Wan, Yong
Chen, Bai-Ling
author_facet Zhao, Sheng-Li
Wen, Zhen-Xing
Mo, Xiao-Yi
Zhang, Xiao-Yan
Li, Hao-Nan
Cheung, Wing-Hoi
Fu, Dan
Zhang, Shi-Hong
Wan, Yong
Chen, Bai-Ling
author_sort Zhao, Sheng-Li
collection PubMed
description Objective: Postmenopausal osteoporosis (PMOP), a chronic systemic metabolic disease prevalent in middle-aged and elderly women, heavily relies on bone mineral density (BMD) measurement as the diagnostic indicator. In this study, we investigated serum microRNAs (miRNAs) as a possible screening tool for PMOP. Methods: This investigation recruited 83 eligible participants from 795 community-dwelling postmenopausal women between June 2020 and August 2021. The miRNA expression profiles in the serum of PMOP patients were evaluated via miRNA microarray (six PMOP patients and four postmenopausal women without osteoporosis (n-PMOP) as controls). Subsequently, results were verified in independent sample sets (47 PMOP patients and 26 n-PMOP controls) using quantitative real-time PCR. In addition, the target genes and main functions of the differentially expressed miRNAs were explored by bioinformatics analysis. Results: Four highly expressed miRNAs in the serum of patients (hsa-miR-144-5p, hsa-miR-506-3p, hsa-miR-8068, and hsa-miR-6851-3p) showed acceptable disease-independent discrimination performance (area under the curve range: 0.747–0.902) in the training set and verification set, outperforming traditional bone turnover markers. Among four key miRNAs, hsa-miR-144-5p is the only one that can simultaneously predict changes in BMD in lumbar spine 1–4, total hip, and femoral neck (β = −0.265, p = 0.022; β = −0.301, p = 0.005; and β = −0.324, p = 0.003, respectively). Bioinformatics analysis suggested that the differentially expressed miRNAs were targeted mainly to YY1, VIM, and YWHAE genes, which are extensively involved in bone metabolism processes. Conclusions: Bone-metabolism-related serum miRNAs, such as hsa-miR-144-5p, hsa-miR-506-3p, hsa-miR-8068, and hsa-miR-6851-3p, can be used as novel biomarkers for PMOP diagnosis independent of radiological findings and traditional bone turnover markers. Further study of these miRNAs and their target genes may provide new insights into the epigenetic regulatory mechanisms of the onset and progression of the disease.
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spelling pubmed-96893102022-11-25 Bone-Metabolism-Related Serum microRNAs to Diagnose Osteoporosis in Middle-Aged and Elderly Women Zhao, Sheng-Li Wen, Zhen-Xing Mo, Xiao-Yi Zhang, Xiao-Yan Li, Hao-Nan Cheung, Wing-Hoi Fu, Dan Zhang, Shi-Hong Wan, Yong Chen, Bai-Ling Diagnostics (Basel) Article Objective: Postmenopausal osteoporosis (PMOP), a chronic systemic metabolic disease prevalent in middle-aged and elderly women, heavily relies on bone mineral density (BMD) measurement as the diagnostic indicator. In this study, we investigated serum microRNAs (miRNAs) as a possible screening tool for PMOP. Methods: This investigation recruited 83 eligible participants from 795 community-dwelling postmenopausal women between June 2020 and August 2021. The miRNA expression profiles in the serum of PMOP patients were evaluated via miRNA microarray (six PMOP patients and four postmenopausal women without osteoporosis (n-PMOP) as controls). Subsequently, results were verified in independent sample sets (47 PMOP patients and 26 n-PMOP controls) using quantitative real-time PCR. In addition, the target genes and main functions of the differentially expressed miRNAs were explored by bioinformatics analysis. Results: Four highly expressed miRNAs in the serum of patients (hsa-miR-144-5p, hsa-miR-506-3p, hsa-miR-8068, and hsa-miR-6851-3p) showed acceptable disease-independent discrimination performance (area under the curve range: 0.747–0.902) in the training set and verification set, outperforming traditional bone turnover markers. Among four key miRNAs, hsa-miR-144-5p is the only one that can simultaneously predict changes in BMD in lumbar spine 1–4, total hip, and femoral neck (β = −0.265, p = 0.022; β = −0.301, p = 0.005; and β = −0.324, p = 0.003, respectively). Bioinformatics analysis suggested that the differentially expressed miRNAs were targeted mainly to YY1, VIM, and YWHAE genes, which are extensively involved in bone metabolism processes. Conclusions: Bone-metabolism-related serum miRNAs, such as hsa-miR-144-5p, hsa-miR-506-3p, hsa-miR-8068, and hsa-miR-6851-3p, can be used as novel biomarkers for PMOP diagnosis independent of radiological findings and traditional bone turnover markers. Further study of these miRNAs and their target genes may provide new insights into the epigenetic regulatory mechanisms of the onset and progression of the disease. MDPI 2022-11-19 /pmc/articles/PMC9689310/ /pubmed/36428932 http://dx.doi.org/10.3390/diagnostics12112872 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhao, Sheng-Li
Wen, Zhen-Xing
Mo, Xiao-Yi
Zhang, Xiao-Yan
Li, Hao-Nan
Cheung, Wing-Hoi
Fu, Dan
Zhang, Shi-Hong
Wan, Yong
Chen, Bai-Ling
Bone-Metabolism-Related Serum microRNAs to Diagnose Osteoporosis in Middle-Aged and Elderly Women
title Bone-Metabolism-Related Serum microRNAs to Diagnose Osteoporosis in Middle-Aged and Elderly Women
title_full Bone-Metabolism-Related Serum microRNAs to Diagnose Osteoporosis in Middle-Aged and Elderly Women
title_fullStr Bone-Metabolism-Related Serum microRNAs to Diagnose Osteoporosis in Middle-Aged and Elderly Women
title_full_unstemmed Bone-Metabolism-Related Serum microRNAs to Diagnose Osteoporosis in Middle-Aged and Elderly Women
title_short Bone-Metabolism-Related Serum microRNAs to Diagnose Osteoporosis in Middle-Aged and Elderly Women
title_sort bone-metabolism-related serum micrornas to diagnose osteoporosis in middle-aged and elderly women
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9689310/
https://www.ncbi.nlm.nih.gov/pubmed/36428932
http://dx.doi.org/10.3390/diagnostics12112872
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