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

Zhao, Shengli; Wen, Zhenxing; Mo, Xiaoyi; Zhang, Xiaoyan; Li, Haonan; Cheung, Wing-Hoi; Fu, Dan; Zhang, Shihong; Wan, Yong; Chen, Bailing

doi:10.3390/diagnostics12112872

Cited by 10 publications

(7 citation statements)

References 43 publications

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“…As such, miR-144-5p has been shown to be upregulated in children with T1DM at early disease stages, but not at later stages, and similarly, miR-144-5p was found to be upregulated in post-menopausal women with osteoporosis, but not with osteopenia. 20 , 55 Similar patterns were observed for miR-21 in plasma samples, 21 indicating potential disease-stage-related miRNA expressions. However, it should be noted that other studies also did not find an association of those miRNAs with parameters of diabetes control or bone turnover markers, suggesting only limited use of these miRNAs as biomarkers for diabetic bone disease.…”

Section: Discussionsupporting

confidence: 59%

MiR-144-5p and miR-21-5p do not drive bone disease in a mouse model of type 1 diabetes mellitus

Daamouch,

Blüher,

Vázquez

et al. 2024

JBMR Plus

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The increased risk of fractures in patients with type 1 diabetes mellitus (T1DM) is nowadays well recognized. However, the exact mechanism of action of diabetic bone disease has not been fully elucidated. MicroRNAs (miRNAs) are gene regulators that operate post-transcriptionally and have been implicated in the development of various metabolic disorders including T1DM. Previous studies have implicated a role for miR-144-5p and miR-21-5p, which are involved in controlling oxidative stress by targeting Nrf2, in T1DM. To date, it is unclear whether miR-144-5p and miR-21-5p affect bone health in T1DM. Thus, this study aimed to investigate the influence of miR-144-5p and miR-21-5p knockdown in the development of bone disease in T1DM male mice. Therefore, T1DM was induced in 10-week-old male mice using streptozotocin (STZ). One week later, after development of hyperglycemia, antagomir-144-5p and antagomir-21-5p or their non-targeting control were administered at 10 mg/kg BW once a week until the end of the experiment. At 14 weeks of age, glucose levels, bone and fat mass were analyzed. The results revealed that treating T1DM male mice with antagomir-144-5p and antagomir-21-5p did not protect against diabetes development or bone loss, despite the successful down-regulation of the miRNAs and the normalization of Nrf2 mRNA levels in bone tissue. Histological and serological parameters of bone formation or resorption were not altered by the antagomir treatment. Finally, we measured the expression of miRNA-144-5p or miRNA-21-5p in the serum of 30 individuals with T1DM and compared them to non-diabetic controls, but did not find an altered expression of either miRNA. In conclusion, the knockdown of miR-144-5p and miR-21-5p does not affect STZ-induced diabetes development or loss of bone mass in male mice. However, it does normalize expression of the anti-oxidant factor Nrf2 in diabetic bone tissue.

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Section: Discussionsupporting

confidence: 59%

MiR-144-5p and miR-21-5p do not drive bone disease in a mouse model of type 1 diabetes mellitus

Daamouch,

Blüher,

Vázquez

et al. 2024

JBMR Plus

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“…Numerous studies have shown that miRNAs are associated with osteoporosis [32,39]. MiRNAs are small noncoding RNA molecules of about 20 nucleotides implicated in posttranscriptional gene expression regulation through targeting of mRNAs [4].…”

Section: Discussionmentioning

confidence: 99%

miR-595/Cldnd1 axis: a potential risk factor for bone loss in postmenopausal women with hip osteoporotic fracture

Jingyue,

Peixin,

Xiao

2024

Preprint

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Background Recently researches have reported that miRNA and its target genes are associated with osteoporosis. MiRNAs/mRNA axis might be an potential diagnostic marker for osteoporosis. Purposes The aim of this study is to explore the potential miRNA and mRNA markers by bioinformatics method and clinical analysis. Patients and Methods The miRNA expression profiles were obtained from GSE74209, GSE64433 and GSE115773 in Gene expression Omnibus (GEO). The mRNA expression profiles were obtained from GSE100609. Wayne intersection were used to explore the different expressed miRNAs (DE-miRs). Select the miRNA with the highest Fold Change for subsequent research. Screening of miRNA target genes using TargetScan and miRDB tools. GO and KEGG analyses of target genes (TGs) function were performed. Validate the selected TGs in the GSE100609. We collected female patients with femural intertrochanteric fractures from July 1, 2023 to October 31, 2023. Patient's bone marrow and clinical data were collected. MiRNA and the target mRNA differentially expressed in bone marrow were verified through RT-qPCR. All data were subjected to Shapiro-Wilk test. Using Pearson or Spearman test to detect the correlation between various indicators, and then incorporating indicators related to bone density into multiple linear regression equations. Partial correlation analysis was used to analyze the correlation between the final indicators and bone density. Results A total of 140 DE-miRs were identified between high bone density and low bone density women. Set the fold change to “>1” and ultimately include 5 miRNAs. Using miR-595 (highest |log2 FC|) as the subject of subsequent research. 3542 targeted mRNAs were predicted from TargetScan and 362 were from miRDB. 337 TGs were intersected, which were mainly enriched in nucleus. Only Cldnd1 were identified using the GSE100609 dataset. We found that miR-595 was highly expressed in patients with high bone mass, while its target gene Cldnd1 was downregulated. There was a strong collinearity between miR-595 and Cldnd1. Further multiple linear regression analysis showed a high correlation between miR-595 and bone density. Conclusions These data suggest that Cldnd1 might be a downstream factor of miR-595. miR-595/Cldnd1 axis might be an independent risk factor for decreased bone mass.

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“…They also performed bioinformatic analysis, suggesting that expressed miRNAs were targeted to genes such as YY1 , VIM , and YWHAE strongly involved in bone metabolism processes. Importantly, the authors deposited microarray data in the Gene Expression Omnibus (GEO) database [ 21 ]. In turn, in 2023, Al-Rawaf et al showed that miRNA correlated with osteocalcin, bone-specific alkaline phosphatase, and deoxypyridinoline such as miR-21, miR-24, and mir-100 were upregulated, while miR-24a, miR-103-3p, and miR-142-3p were downregulated [ 94 ].…”

Section: Microrna Clinical Application For Osteoporosismentioning

confidence: 99%

“…In addition, recent reports suggest that miRNAs are important for regulating bone formation and homeostasis in the pathogenesis of osteoporosis [ 16 ]— Figure 1 . In addition, miRNAs are present in body fluids, including serum, suggesting that miRNAs could serve as simple biomarkers for osteoporosis [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

The MicroRNAs in the Pathophysiology of Osteoporosis

Trojniak,

Sendera,

Banaś-Ząbczyk

et al. 2024

IJMS

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Globally, osteoporosis is the most common systemic skeletal disease. There are many factors that influence osteoporosis’ development and progression. During the pathogenesis of this disease, bone turnover is imbalanced between resorption and the formation of bone tissue. A growing interest has been devoted to the role that microRNA (miRNA) plays in osteoporosis regulation. A microRNA (miRNA) is a group of small single-stranded RNA molecules involved in regulating gene expression in eukaryotic organisms. As microRNAs (miRNAs) are key regulators of gene expression and can modulate processes related to bone metabolism, they have become increasingly important for studying osteoporosis pathogenesis. The available research suggests that miRNAs play an important role in regulating processes associated with bone metabolism, especially by influencing bone resorption and synthesis. Furthermore, microRNAs can also serve as potential therapeutic targets for osteoporosis, besides being a rapid and specific biomarker.

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

Cited by 10 publications

References 43 publications

MiR-144-5p and miR-21-5p do not drive bone disease in a mouse model of type 1 diabetes mellitus

MiR-144-5p and miR-21-5p do not drive bone disease in a mouse model of type 1 diabetes mellitus

miR-595/Cldnd1 axis: a potential risk factor for bone loss in postmenopausal women with hip osteoporotic fracture

The MicroRNAs in the Pathophysiology of Osteoporosis

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