Analysis of the Bone MicroRNome in Osteoporotic Fractures

Garmilla-Ezquerra, Pablo; Sañudo, Carolina; Delgado‐Calle, Jesús; Pérez-Núñez, María Isabel; Sumillera, Manuel; Riancho, José A.

doi:10.1007/s00223-014-9935-7

Cited by 60 publications

(51 citation statements)

References 33 publications

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“…This underlines the need to validate, in individual samples, the results of the profiling stage. In another study, Garmilla-Ezquerra et al [22], describe a differential expression of 13 miRNAs (nominal P \ 0.05) in primary osteoblasts from BF patients and osteoarthritic controls, as in the present study. Although they try to replicate the miR-210 (nominal P = 0.06), because it seems to have been associated with osteoblast activity in human bone samples in a recent study [23], no statistical significance arises at the validation stage.…”

Section: Discussionsupporting

confidence: 57%

Serum Circulating MicroRNAs as Biomarkers of Osteoporotic Fracture

et al. 2015

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Osteoporosis is a common skeletal disorder characterized by increased risk of bone fracture (BF) due to fragility. BFs, particularly hip fracture, are a major concern in health care because of the associated morbidity and mortality, mainly in the elderly. Lately the involvement of epigenetic mechanisms in the pathophysiology of many diseases has been recognized. In this context, the identification of microRNAs (miRNAs) specific to BF should represent a substantial step forward in diagnostics and therapeutics. The present study aimed to identify specific miRNAs in osteoporotic BF patients compared to those in osteoarthritic controls. In the profiling stage, total RNA was extracted from serum, two pools were prepared, and then retro-transcribed in triplicate. Levels of 179 serum miRNAs were analyzed by real-time PCR, and 42 of them showed significance (P < 0.05), and 12 passed the false discovery rate test for multiple comparisons. Six miRNAs were selected for the replication stage and individually analyzed in sera from 15 BF patients and 12 controls. Results showed that 3 miRNAs (miR-122-5p, miR-125b-5p, and miR-21-5p) were valuable upregulated biomarkers in BF with respect to controls and, significantly, their levels were not affected by hemolysis. For miR-21-5p, the difference detected between groups was independent of age (P = 0.005) and its levels correlated to those of CTx (r = 0.76; P < 0.00001), a marker of bone resorption. In conclusion, several miRNAs may be biomarkers of BF, particularly miR-21-5p. Further studies are needed in order to better characterize the levels of these miRNAs in other bone diseases and to elucidate the mechanism involved in the association of these three miRNAs with osteoporotic BF.

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Section: Discussionsupporting

confidence: 57%

Serum Circulating MicroRNAs as Biomarkers of Osteoporotic Fracture

et al. 2015

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“…A more comprehensive study examined the expression of 760 miRNAs in trabecular bone samples obtained from the femoral heads of patients with osteoporotic hip fractures and showed that 13 miRNAs (let‐7i, miR‐135a, miR‐137, miR‐181a‐2, miR‐187, miR‐193a‐3p, miR‐214, miR‐330‐5p, miR‐518f, miR‐519d, miR‐524, miR‐636, and miR‐643) displayed significant differences: seven with higher levels in bones from osteoporotic patients and the other six in the nonfractured bones. The authors selected six miRNAs (miR‐187, miR‐193a‐3p, miR‐214, miR518f, miR‐636, and miR‐210) for further analysis and found that miR‐187 levels were 5.3‐fold higher in the nonfracture group, whereas miR‐518f levels were 8.6‐fold higher in bones from fractures of osteoporotic patients; the other four did not show any statistical differences between the two groups …”

Section: Mirna Profiling and Fracturesmentioning

confidence: 99%

“…The authors selected six miRNAs (miR-187, miR-193a-3p, miR-214, miR518f, miR-636, and miR-210) for further analysis and found that miR-187 levels were 5.3-fold higher in the nonfracture group, whereas miR-518f levels were 8.6-fold higher in bones from fractures of osteoporotic patients; the other four did not show any statistical differences between the two groups. (31) More recently, screening serum levels of 139 patients, (32) which included controls, osteopenic (with and without fractures), and osteoporotic (with and without fracture), for the presence of circulating miRNAs, found miR122-5p and miR-4516 to be present at significantly different levels between nonosteoporotic control, osteopenic, and osteoporosis patients. Specifically, miR-122-5p levels were much lower in osteoporosis patients compared with nonosteoporotic control and osteopenic patients.…”

Section: Mirna Profiling and Fracturesmentioning

confidence: 99%

“…Significantly upregulated in serum (30) Osteoporotic fractures miR-187 Significantly downregulated in bone (31) miR-518f Significantly upregulated in bone Osteoporoticfractures miR-122-5p, miR-4516 Significantly downregulated in serum (32) Osteoporoticfractures miR-23b-3p miR-140-3p, miR-885-5p, miR-17-5p, miR-1227-3p, miR-139-5p and miR-197-3p…”

Section: Mirnas and Fracture Repairmentioning

confidence: 99%

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The Therapeutic Potential of MicroRNAs as Orthobiologics for Skeletal Fractures

Hadjiargyrou

Komatsu

2019

Journal of Bone and Mineral Research

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The repair of a fractured bone is critical to the well‐being of humans. Failure of the repair process to proceed normally can lead to complicated fractures, exemplified by either a delay in union or a complete nonunion. Both of these conditions lead to pain, the possibility of additional surgery, and impairment of life quality. Additionally, work productivity decreases, income is reduced, and treatment costs increase, resulting in financial hardship. Thus, developing effective treatments for these difficult fractures or even accelerating the normal physiological repair process is warranted. Accumulating evidence shows that microRNAs (miRNAs), small noncoding RNAs, can serve as key regulatory molecules of fracture repair. In this review, a brief description of the fracture repair process and miRNA biogenesis is presented, as well as a summary of our current knowledge of the involvement of miRNAs in physiological fracture repair, osteoporotic fractures, and bone defect healing. Further, miRNA polymorphisms associated with fractures, miRNA presence in exosomes, and miRNAs as potential therapeutic orthobiologics are also discussed. This is a timely review as several miRNA‐based therapeutics have recently entered clinical trials for nonskeletal applications and thus it is incumbent upon bone researchers to explore whether miRNAs can become the next class of orthobiologics for the treatment of skeletal fractures.

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“…177 Yavropoulou et al analyzed circulating miRNAs to identify potential biomarkers for osteoporosis and osteoporotic fractures. 178 Five miRNAs were significantly deregulated in the serum of patients with low bone mass compared with controls, two of which ( miR-29a and miR-2861 ), have already been discussed in this review.…”

Section: Mirnas Associated With Skeletal Disease and Other Orthopaedimentioning

confidence: 99%

MicroRNAs in orthopaedic research: Disease associations, potential therapeutic applications, and perspectives

McAlinden

2017

Journal Orthopaedic Research

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MicroRNAs (miRNAs) are small non-coding RNAs that function to control many cellular processes by their ability to suppress expression of specific target genes. Tens to hundreds of target genes may be affected by one miRNA, thereby resulting in modulation of multiple pathways in any given cell type. Therefore, altered expression of miRNAs (i.e., during tissue development or in scenarios of disease or cellular stress) can have a profound impact on processes regulating cell differentiation, metabolism, proliferation, or apoptosis, for example. Over the past 5-10 years, thousands of reports have been published on miRNAs in cartilage and bone biology or disease, thus highlighting the significance of these non-coding RNAs in regulating skeletal development and homeostasis. For the purpose of this review, we will focus on miRNAs or miRNA families that have demonstrated function in vivo within the context of cartilage, bone or other orthopaedicrelated tissues (excluding muscle). Specifically, we will discuss studies that have utilized miRNA transgenic mouse models or in vivo approaches to target a miRNA with the aim of altering conditions such as osteoarthritis, osteoporosis and bone fractures in rodents. We will not discuss miRNAs in the context skeletal cancers since this topic is worthy of a review of its own. Overall, we aim to provide a comprehensive description of where the field currently stands with respect to the therapeutic potential of specific miRNAs to treat orthopaedic conditions and current technologies to target and modify miRNA function in vivo. KeywordsMicroRNAs (miRNAs); cartilage; bone; skeletal development; osteoarthritis MicroRNA (miRNAs) are small non-coding RNA molecules (typically 19-24 nucleotides in length) that function in RNA silencing and post-transcriptional regulation (suppression) of gene expression. 1 While the majority of miRNAs are located within the cell, some miRNAs, commonly known as circulating miRNA or extracellular miRNA, have also been detected outside the cell in the extracellular matrix, in various biological fluids, or in cell culture. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript miRNAs were first discovered over 20 years ago in the nematode Caenorhabditis elegans with the identification of the developmental regulator lin-4. 3 Since then, thousands of miRNAs have been identified and investigated, with a wide distribution in animals, plants, and viruses. 4 MicroRNAs are ubiquitously expressed in different organisms, and many of them are phylogenetically conserved. 5 To date, over 28,000 miR-NAs from various species are listed in the miRBase website (http://www.mirbase.org). Specifically, 2,588 mature miRNAs have been identified in humans and 1,915 mature miRNAs have been reported in mice.With respect to miRNA biosynthesis, transcription of miRNA genes that are located either intergenically or intragenically is mediated primarily by RNA polymerase II in eukaryotes, although RNA polymerase III has also been shown to transcrib...

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Analysis of the Bone MicroRNome in Osteoporotic Fractures

Cited by 60 publications

References 33 publications

Serum Circulating MicroRNAs as Biomarkers of Osteoporotic Fracture

Serum Circulating MicroRNAs as Biomarkers of Osteoporotic Fracture

The Therapeutic Potential of MicroRNAs as Orthobiologics for Skeletal Fractures

MicroRNAs in orthopaedic research: Disease associations, potential therapeutic applications, and perspectives

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