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

<b>Objective</b>: 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 possib...

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Main Authors: Sheng-Li Zhao, Zhen-Xing Wen, Xiao-Yi Mo, Xiao-Yan Zhang, Hao-Nan Li, Wing-Hoi Cheung, Dan Fu, Shi-Hong Zhang, Yong Wan, Bai-Ling Chen
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Diagnostics
Subjects:
Online Access:https://www.mdpi.com/2075-4418/12/11/2872
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author Sheng-Li Zhao
Zhen-Xing Wen
Xiao-Yi Mo
Xiao-Yan Zhang
Hao-Nan Li
Wing-Hoi Cheung
Dan Fu
Shi-Hong Zhang
Yong Wan
Bai-Ling Chen
author_facet Sheng-Li Zhao
Zhen-Xing Wen
Xiao-Yi Mo
Xiao-Yan Zhang
Hao-Nan Li
Wing-Hoi Cheung
Dan Fu
Shi-Hong Zhang
Yong Wan
Bai-Ling Chen
author_sort Sheng-Li Zhao
collection DOAJ
description <b>Objective</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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 (<i>β</i> = −0.265, <i>p</i> = 0.022; <i>β</i> = −0.301, <i>p</i> = 0.005; and <i>β</i> = −0.324, <i>p</i> = 0.003, respectively). Bioinformatics analysis suggested that the differentially expressed miRNAs were targeted mainly to <i>YY1</i>, <i>VIM</i>, and <i>YWHAE</i> genes, which are extensively involved in bone metabolism processes. <b>Conclusions</b>: 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 doaj.art-fe88f94f55c940feb15f3f4fb7a9f4e92023-11-24T08:05:38ZengMDPI AGDiagnostics2075-44182022-11-011211287210.3390/diagnostics12112872Bone-Metabolism-Related Serum microRNAs to Diagnose Osteoporosis in Middle-Aged and Elderly WomenSheng-Li Zhao0Zhen-Xing Wen1Xiao-Yi Mo2Xiao-Yan Zhang3Hao-Nan Li4Wing-Hoi Cheung5Dan Fu6Shi-Hong Zhang7Yong Wan8Bai-Ling Chen9Department of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Orthopaedics, Guangzhou First People’s Hospital, Guangzhou 510180, ChinaDepartment of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Orthopaedics and Traumatology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR 999077, ChinaDepartment of Orthopedics, Kiang Wu Hospital, Macau SAR 999078, ChinaDepartment of Laboratry Medicine, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Spine Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China<b>Objective</b>: 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. <b>Methods</b>: 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. <b>Results</b>: 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 (<i>β</i> = −0.265, <i>p</i> = 0.022; <i>β</i> = −0.301, <i>p</i> = 0.005; and <i>β</i> = −0.324, <i>p</i> = 0.003, respectively). Bioinformatics analysis suggested that the differentially expressed miRNAs were targeted mainly to <i>YY1</i>, <i>VIM</i>, and <i>YWHAE</i> genes, which are extensively involved in bone metabolism processes. <b>Conclusions</b>: 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.https://www.mdpi.com/2075-4418/12/11/2872postmenopausal osteoporosisserummicroRNAdiagnosisepigenetics
spellingShingle Sheng-Li Zhao
Zhen-Xing Wen
Xiao-Yi Mo
Xiao-Yan Zhang
Hao-Nan Li
Wing-Hoi Cheung
Dan Fu
Shi-Hong Zhang
Yong Wan
Bai-Ling Chen
Bone-Metabolism-Related Serum microRNAs to Diagnose Osteoporosis in Middle-Aged and Elderly Women
Diagnostics
postmenopausal osteoporosis
serum
microRNA
diagnosis
epigenetics
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 postmenopausal osteoporosis
serum
microRNA
diagnosis
epigenetics
url https://www.mdpi.com/2075-4418/12/11/2872
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