Circulating microRNA Signatures in Patients With Idiopathic and Postmenopausal Osteoporosis and Fragility Fractures

Kocijan, Roland; Muschitz, Christian; Geiger, Elisabeth; Skalicky, Susanna; Baierl, Andreas; Dormann, R.; Plachel, Fabian; Feichtinger, Xaver; Heimel, Patrick; Fahrleitner‐Pammer, Astrid; Grillari, Johannes; Redl, Heinz; Resch, Heinrich; Hackl, Matthias

doi:10.1210/jc.2016-2365

Cited by 165 publications

(163 citation statements)

References 37 publications

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“…Our study is strengthened by the extremely careful in control of potentially confounding characteristics among bone samples in terms of age, sex, BMI and metabolic diseases highly prevalent in elderly population 15, 16 . Moreover, we excluded from the study samples from patients treated with hormones and other anti-osteoporotic drugs that could alter the miRNA expression in bone cells 17 .…”

Section: Discussionmentioning

confidence: 85%

SNPs in bone-related miRNAs are associated with the osteoporotic phenotype

De-Ugarte

Caro-Molina

Rodríguez-Sanz

et al. 2017

Sci Rep

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Biogenesis and function of microRNAs can be influenced by genetic variants in the pri-miRNA sequences leading to phenotypic variability. This study aims to identify single nucleotide polymorphisms (SNPs) affecting the expression levels of bone-related mature microRNAs and thus, triggering an osteoporotic phenotype. An association analysis of SNPs located in pri-miRNA sequences with bone mineral density (BMD) was performed in the OSTEOMED2 cohort (n = 2183). Functional studies were performed for assessing the role of BMD-associated miRNAs in bone cells. Two SNPs, rs6430498 in the miR-3679 and rs12512664 in the miR-4274, were significantly associated with femoral neck BMD. Further, we measured these BMD-associated microRNAs in trabecular bone from osteoporotic hip fractures comparing to non-osteoporotic bone by qPCR. Both microRNAs were found overexpressed in fractured bone. Increased matrix mineralization was observed after miR-3679-3p inhibition in human osteoblastic cells. Finally, genotypes of rs6430498 and rs12512664 were correlated with expression levels of miR-3679 and miR-4274, respectively, in osteoblasts. In both cases, the allele that generated higher microRNA expression levels was associated with lower BMD values. In conclusion, two osteoblast-expressed microRNAs, miR-3679 and miR-4274, were associated with BMD; their overexpression could contribute to the osteoporotic phenotype. These findings open new areas for the study of bone disorders.

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Section: Discussionmentioning

confidence: 85%

SNPs in bone-related miRNAs are associated with the osteoporotic phenotype

De-Ugarte

Caro-Molina

Rodríguez-Sanz

et al. 2017

Sci Rep

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“…MiR-93-5p was also shown to be downregulated in serum of osteoporotic patients with low traumatic fractures and has also been associated with bone mineral density [34]. …”

Section: Discussionmentioning

confidence: 99%

MicroRNAs 223-3p and 93-5p in patients with chronic kidney disease before and after renal transplantation

Ulbing

Kirsch

Leber

et al. 2017

Bone

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Chronic kidney disease (CKD) is associated with a multifactorial dysregulation of bone and vascular calcification and closely linked to increased cardiovascular mortality and concomitant bone disease. We aimed to investigate specific microRNA (miRNA) signatures in CKD patients to find indicators for vascular calcification and/or bone mineralization changes during CKD and after kidney transplantation (KT). A miRNA array was used to investigate serum miRNA profiles in CKD patients, then selected miRNAs were quantified in a validation cohort comprising 73 patients in CKD stages 3 to 5, 67 CKD patients after KT, and 36 healthy controls. A spectrum of biochemical parameters including markers for kidney function, inflammation, glucose, and mineral metabolism was determined. The relative expression of miR-223-3p and miR-93-5p was down-regulated in patients with CKD stage 4 and 5 compared to healthy controls. This down-regulation disappeared after kidney transplantation even when lower glomerular filtration rates (eGFR) persisted. MiR-223-3p and miR-93-5p were associated with interleukin-6 (IL-6) and eGFR levels, and by trend with interleukin-8 (IL-8), C-peptide, hematocrit, and parathyroid hormone (PTH). This study contributes new knowledge of serum miRNA expression profiles in CKD, potentially reflecting pathophysiological changes of bone and calcification pathways associated with inflammation, vascular calcification, mineral and glucose metabolism. Identified miRNA signatures can contribute to future risk markers or future therapeutic targets in bone and kidney disease.

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“…MicroRNAs (miRNAs) are evolutionarily conserved, small (~22 nucleotides), singlestranded non-coding RNAs that silence the expression of specific gene by base-pairing to the 3'-untranslated regions of target mRNAs on post-transcriptional level [3][4][5]. At present, numerous studies have indicated that miRNA was a crucial component in the development of osteoporosis [6][7][8][9][10][11]. For example, miR-34a blocks osteoporosis by inhibiting Tgif2 [12]; miRNA-148a regulates osteoclastogenesis via targeting MAFB [13]; and miRNA-142-3p induces cell death in osteoclasts depending on RANKL [14].…”

Section: Introductionmentioning

confidence: 99%

MiR-124 Attenuates Osteoclastogenic Differentiation of Bone Marrow Monocytes Via Targeting Rab27a

Tang¹,

Yin²,

Liu³

et al. 2017

Cell Physiol Biochem

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Background/Aims: With the aging population increases, senile osteoporosis has become a global public health problem. Previous evidence has shown that miR-124 has important effects on the occurrence and development of osteoporosis. However, the role of miR-124 in the process of osteoclastogenesis is still obscure. Methods: First of all, we measured the expression level of miR-124 in bone marrow monocytes (BMMs) of osteoporotic mice (ovariectomized mice: OVX). Next, we evaluated the alteration of miR-124 during osteoclast differentiation of BMMs. Then, BMMs were transfected with miR-124 mimics or inhibitors to explore the influences of miR-124 on osteoclast differentiation of BMMs in vitro. Furthermore, bioinformatics analysis and luciferase reporter assay were performed for prediction and identification of the target of miR-124. Results: BMMs from OVX mice exhibited lower expression of miR-124 compared with Sham mice. Additionally, miR-124 was down-regulated when BMMs differentiated into osteoclasts. In addition, inhibition of miR-124 promoted BMMs differentiated into osteoclasts in vitro, whereas overexpression of miR-124 attenuated this procedure, demonstrated by increased expression of osteoclast specific genes and TRAP staining. Furthermore, Rab27a was confirmed to be the direct target of miR-124 by bioinformatics, Western blot and luciferase reporter assay analysis. Conclusion: Our findings revealed that miR-124 has an important role in osteoclastogenesis via targeting Rab27a. Thus, targeting miR-124 promises a therapeutic potential in the treatment of osteoporosis.

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Circulating microRNA Signatures in Patients With Idiopathic and Postmenopausal Osteoporosis and Fragility Fractures

Cited by 165 publications

References 37 publications

SNPs in bone-related miRNAs are associated with the osteoporotic phenotype

SNPs in bone-related miRNAs are associated with the osteoporotic phenotype

MicroRNAs 223-3p and 93-5p in patients with chronic kidney disease before and after renal transplantation

MiR-124 Attenuates Osteoclastogenic Differentiation of Bone Marrow Monocytes Via Targeting Rab27a

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