Circulating MicroRNAs as Biomarkers of Osteoporosis and Fragility Fractures

Ciuffi, Simone; Marini, Francesca; Fossi, Caterina; Donati, Simone; Giusti, Francesca; Botta, Annalisa; Masi, Laura; Isaia, Giancarlo; Marcocci, Claudio; Migliaccio, Silvia; Minisola, Salvatore; Nuti, Ranuccio; Tarantino, Umberto; Iantomasi, Teresa; Brandi, Maria Luisa

doi:10.1210/clinem/dgac293

Cited by 11 publications

(9 citation statements)

References 69 publications

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“…In addition, miRNAs modulate the expression of very important genes involved in the recruitment of various bone cells in the osteogenic process, and facilitate mineralization by affecting the maturation of the collagen fibrillar matrix [ 33 , 34 ]. However, the dysregulation of miRNA expression also plays an important role in the development of disease [ 35 ], and can be involved in bone-related diseases and disorders such as osteoporosis [ 32 , 36 , 37 ]. ROS can down- or upregulate the expression of miRNAs and vice versa, and miRNAs can affect oxidative stress by inhibiting or stimulating ROS production [ 38 ].…”

Section: Introductionmentioning

confidence: 99%

Oxidative Stress and Inflammation in Osteoporosis: Molecular Mechanisms Involved and the Relationship with microRNAs

Iantomasi

Romagnoli

Palmini

et al. 2023

IJMS

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Osteoporosis is characterized by the alteration of bone homeostasis due to an imbalance between osteoclastic bone resorption and osteoblastic bone formation. Estrogen deficiency causes bone loss and postmenopausal osteoporosis, the pathogenesis of which also involves oxidative stress, inflammatory processes, and the dysregulation of the expression of microRNAs (miRNAs) that control gene expression at post-transcriptional levels. Oxidative stress, due to an increase in reactive oxygen species (ROS), proinflammatory mediators and altered levels of miRNAs enhance osteoclastogenesis and reduce osteoblastogenesis through mechanisms involving the activation of MAPK and transcription factors. The present review summarizes the principal molecular mechanisms involved in the role of ROS and proinflammatory cytokines on osteoporosis. Moreover, it highlights the interplay among altered miRNA levels, oxidative stress, and an inflammatory state. In fact, ROS, by activating the transcriptional factors, can affect miRNA expression, and miRNAs can regulate ROS production and inflammatory processes. Therefore, the present review should help in identifying targets for the development of new therapeutic approaches to osteoporotic treatment and improve the quality of life of patients.

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Section: Introductionmentioning

confidence: 99%

Oxidative Stress and Inflammation in Osteoporosis: Molecular Mechanisms Involved and the Relationship with microRNAs

Iantomasi

Romagnoli

Palmini

et al. 2023

IJMS

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“…Detections of circulating microRNAs (miRNAs) as potential biomarkers for the risk of osteoporosis and subsequent fractures by next-generation sequencing (NGS) and global miRNA expression have recently attracted much attention [ 9 ]. miRNAs have the ability to post-transcriptionally regulate and silence target gene expression and thus play osteoclast differentiation and survival, as well as osteoblast-to-osteoclast communication [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Circulating miR-340-5p and miR-506-3p as Two Osteo-miRNAs for Predicting Osteoporosis in a Cohort of Postmenopausal Women

Lü

Cao

Hu³

2023

Journal of Environmental and Public Health

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Objective. An increasing risk of developing osteoporosis which is characterized by bone production weakness and microarchitectural deterioration is found among postmenopausal women. MicroRNAs (miRNAs) are secreted into the circulation from cells of various tissues in response to local disease severity including bone diseases. Herein, we set out to identify candidate miRNAs predictable for osteoporosis incidence in postmenopausal elderly women. Methods. The circulating miRNA expression profiles deposited in the dataset accessioned as GSE201543 were downloaded from the GEO database. The study included 176 postmenopausal women who underwent BMD testing, including 96 women reporting osteoporosis and 70 women reporting normal BMD. All subjects were submitted their serum samples for measurements of bone metabolism markers. Results. The miRNA expression profiles of the GSE201543 dataset were differentially analyzed and found 97 miRNAs being upregulated concomitantly with 31 miRNAs being downregulated in the serum samples between osteoporotic postmenopausal women and postmenopausal women with normal BMD. Osteoporotic postmenopausal women were demonstrated with elevated serum levels of miR-340-5p and miR-506-3p when compared to normal postmenopausal women. Pearson correlation analysis demonstrated that circulating miR-340-5p and miR-506-3p expressions were increased as BAP, β-CTx, and PINP levels increased, but osteocalcin and 25-(OH)VitD levels are declined in osteoporotic postmenopausal women. Results of the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) showed circulating miR-340-5p and miR-506-3p expressions alone or combined together produced 0.843 AUC, 0.851 AUC, and 0.935 AUC, respectively, when used to predict the incidence of osteoporosis in postmenopausal women. Conclusion. Our work suggested that circulating miR-340-5p and miR-506-3p function as osteo-miRNAs in postmenopausal women and may serve as potential noninvasive biomarkers for the incidence of osteoporosis in postmenopausal women.

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“…Some studies (17%) recruited younger participants in healthy control groups [ 38 , 41 , 42 , 44 , 47 , 59 , 60 , 71 , 78 ] and did not match for age, causing potential selection bias. Almost all the studies considered female osteoporotic and sarcopenic patients (76%), but 14/59 studies also included male patients [ 34 , 38 , 50 , 52 , 53 , 58 , 59 , 60 , 61 , 62 , 66 , 73 , 77 , 82 , 83 ]. Twelve studies on osteoporosis and two on sarcopenia did not state sex.…”

Section: Resultsmentioning

confidence: 99%

“…MiR-23a and its -3p form were up-regulated in four studies [ 32 , 57 , 59 , 75 ] and down-regulated in two studies [ 34 , 70 ]. Ciuffi et al [ 34 ], in their prospective multicenter study, measured miRs by using a next-generation sequencing -based prescreening profile approach considering not only female patients but also osteopenic and/or osteoporosis male patients, showing the deregulated serum levels of miR-23a-3p in osteoporotic patients as well as their relationship with bone quality parameters and sensitivity/specificity in distinguishing osteoporotic patients from normal BMD subjects. Yavropoulou et al [ 70 ] also showed deregulated serum level of miR-23a in patients with low bone mass compared with healthy controls.…”

Section: Resultsmentioning

confidence: 99%

Sharing Circulating Micro-RNAs between Osteoporosis and Sarcopenia: A Systematic Review

Salamanna

Contartese

Ruffilli

et al. 2023

Life

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Background: Osteosarcopenia, a combination of osteopenia/osteoporosis and sarcopenia, is a common condition among older adults. While numerous studies and meta-analyses have been conducted on osteoporosis biomarkers, biomarker utility in osteosarcopenia still lacks evidence. Here, we carried out a systematic review to explore and analyze the potential clinical of circulating microRNAs (miRs) shared between osteoporosis/osteopenia and sarcopenia. Methods: We performed a systematic review on PubMed, Scopus, and Embase for differentially expressed miRs (p-value < 0.05) in (i) osteoporosis and (ii) sarcopenia. Following screening for title and abstract and deduplication, 83 studies on osteoporosis and 11 on sarcopenia were identified for full-text screening. Full-text screening identified 54 studies on osteoporosis, 4 on sarcopenia, and 1 on both osteoporosis and sarcopenia. Results: A total of 69 miRs were identified for osteoporosis and 14 for sarcopenia. There were 9 shared miRs, with evidence of dysregulation (up- or down-regulation), in both osteoporosis and sarcopenia: miR-23a-3p, miR-29a, miR-93, miR-133a and b, miR-155, miR-206, miR-208, miR-222, and miR-328, with functions and targets implicated in the pathogenesis of osteosarcopenia. However, there was little agreement in the results across studies and insufficient data for miRs in sarcopenia, and only three miRs, miR-155, miR-206, and miR-328, showed the same direction of dysregulation (down-regulation) in both osteoporosis and sarcopenia. Additionally, for most identified miRs there has been no replication by more than one study, and this is particularly true for all miRs analyzed in sarcopenia. The study quality was typically rated intermediate/high risk of bias. The large heterogeneity of the studies made it impossible to perform a meta-analysis. Conclusions: The findings of this review are particularly novel, as miRs have not yet been explored in the context of osteosarcopenia. The dysregulation of miRs identified in this review may provide important clues to better understand the pathogenesis of osteosarcopenia, while also laying the foundations for further studies to lead to effective screening, monitoring, or treatment strategies.

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Circulating MicroRNAs as Biomarkers of Osteoporosis and Fragility Fractures

Cited by 11 publications

References 69 publications

Oxidative Stress and Inflammation in Osteoporosis: Molecular Mechanisms Involved and the Relationship with microRNAs

Oxidative Stress and Inflammation in Osteoporosis: Molecular Mechanisms Involved and the Relationship with microRNAs

Circulating miR-340-5p and miR-506-3p as Two Osteo-miRNAs for Predicting Osteoporosis in a Cohort of Postmenopausal Women

Sharing Circulating Micro-RNAs between Osteoporosis and Sarcopenia: A Systematic Review

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