scholarly journals The Role of Extracellular Vesicles (EVs) in the Epigenetic Regulation of Bone Metabolism and Osteoporosis

2020 ◽  
Vol 21 (22) ◽  
pp. 8682 ◽  
Author(s):  
Maurizio Muraca ◽  
Alfredo Cappariello
Keyword(s):  
Bone Metabolism ◽  
Extracellular Vesicles ◽  
Epigenetic Regulation ◽  
Bone Cells ◽  
Disease Onset ◽  
Powerful Means ◽  
Fine Regulation ◽  
Non Coding Rnas ◽  
Epigenetic Processes

Extracellular vesicles (EVs) are complex phospholipidic structures actively released by cells. EVs are recognized as powerful means of intercellular communication since they contain many signaling molecules (including lipids, proteins, and nucleic acids). In parallel, changes in epigenetic processes can lead to changes in gene function and finally lead to disease onset and progression. Recent breakthroughs have revealed the complex roles of non-coding RNAs (microRNAs (miRNAs) and long non-coding RNAs (lncRNAs)) in epigenetic regulation. Moreover, a substantial body of evidence demonstrates that non-coding RNAs can be shuttled among the cells and tissues via EVs, allowing non-coding RNAs to reach distant cells and exert systemic effects. Resident bone cells, including osteoclasts, osteoblasts, osteocytes, and endothelial cells, are tightly regulated by non-coding RNAs, and many of them can be exported from the cells to neighboring ones through EVs, triggering pathological conditions. For these reasons, researchers have also started to exploit EVs as a theranostic tool to address osteoporosis. In this review, we summarize some recent findings regarding the EVs’ involvement in the fine regulation of non-coding RNAs in the context of bone metabolism and osteoporosis.

scholarly journals The Role of MicroRNAs in Bone Metabolism and Disease

2020 ◽  
Vol 21 (17) ◽  
pp. 6081 ◽  
Author(s):  
Yongguang Gao ◽  
Suryaji Patil ◽  
Airong Qian
Keyword(s):  
Bone Metabolism ◽  
Bone Cells ◽  
Low Bone Mass ◽  
Mineral Density ◽  
Cellular Processes ◽  
Receptor Modulator ◽  
Non Coding Rnas ◽  
Necrosis Of Femoral Head

Bone metabolism is an intricate process involving various bone cells, signaling pathways, cytokines, hormones, growth factors, etc., and the slightest deviation can result in various bone disorders including osteoporosis, arthropathy, and avascular necrosis of femoral head. Osteoporosis is one of the most prevalent disorders affecting the skeleton, which is characterized by low bone mass and bone mineral density caused by the disruption in the balanced process of bone formation and bone resorption. The current pharmaceutical treatments such as bisphosphonates, selective estrogen receptor modulator, calcitonin, teriparatide, etc., could decrease the risk of fractures but have side-effects that have limited their long term applications. MicroRNAs (miRNAs) are one of many non-coding RNAs. These are single-stranded with a length of 19–25 nucleotides and can influence various cellular processes and play an important role in various diseases. Therefore, in this article, we review the different functions of different miRNA in bone metabolism and osteoporosis to understand their mechanism of action for the development of possible therapeutics.

scholarly journals Long Non-coding RNAs RN7SK and GAS5 Regulate Macrophage Polarization and Innate Immune Responses

2020 ◽  
Vol 11 ◽  
Author(s):  
Imran Ahmad ◽  
Araceli Valverde ◽  
Raza Ali Naqvi ◽  
Afsar R. Naqvi
Keyword(s):  
Immune Responses ◽  
Epigenetic Regulation ◽  
Innate Immune ◽  
Differentially Expressed ◽  
Immune Functions ◽  
Innate Immune Responses ◽  
Antigen Uptake ◽  
Non Coding Rnas

Macrophages (Mφ) are immune cells that exhibit remarkable functional plasticity. Identification of novel endogenous factors that can regulate plasticity and innate immune functions of Mφ will unravel new strategies to curb immune-related diseases. Long non-coding RNAs (lncRNAs) are a class of endogenous, non-protein coding, regulatory RNAs that are increasingly being associated with various cellular functions and diseases. Despite their ubiquity and abundance, lncRNA-mediated epigenetic regulation of Mφ polarization and innate immune functions is poorly studied. This study elucidates the regulatory role of lncRNAs in monocyte to Mφ differentiation, M1/M2 dichotomy and innate immune responses. Expression profiling of eighty-eight lncRNAs in monocytes and in vitro differentiated M2 Mφ identified seventeen differentially expressed lncRNAs. Based on fold-change and significance, we selected four differentially expressed lncRNAs viz., RN7SK, GAS5, IPW, and ZFAS1 to evaluate their functional impact. LncRNA knockdown was performed on day 3 M2 Mφ and the impact on polarization was assessed on day 7 by surface marker analysis. Knockdown of RN7SK and GAS5 showed downregulation of M2 surface markers (CD163, CD206, or Dectin) and concomitant increase in M1 markers (MHC II or CD23). RN7SK or GAS5 knockdown showed no significant impact on CD163, CD206, or CD23 transcripts. M1/M2 markers were not impacted by IPW or ZFAS1 knockdown. Functional regulation of antigen uptake/processing and phagocytosis, two central innate immune pathways, by candidate lncRNA was assessed in M1/M2 Mφ. Compared to scramble, enhanced antigen uptake and processing were observed in both M1/M2 Mφ transfected with siRNA targeting GAS5 and RN7SK but not IPW and ZFAS1. In addition, knockdown of RN7SK significantly augmented uptake of labelled E. coli in vitro by M1/M2 Mφ, while no significant difference was in GAS5 silencing cells. Together, our results highlight the instrumental role of lncRNA (RN7SK and GAS5)-mediated epigenetic regulation of macrophage differentiation, polarization, and innate immune functions.

Epigenetics of scleroderma: Integrating genetic, ethnic, age, and environmental effects

2019 ◽  
Vol 4 (3) ◽  
pp. 238-250 ◽  
Author(s):  
Paula S Ramos
Keyword(s):  
Systemic Sclerosis ◽  
Epigenetic Regulation ◽  
Environmental Effects ◽  
Genetic Factors ◽  
Cell Types ◽  
Underlying Mechanism ◽  
Epigenome Editing ◽  
Non Coding Rnas ◽  
Epigenetic Editing

Scleroderma or systemic sclerosis is thought to result from the interplay between environmental or non-genetic factors in a genetically susceptible individual. Epigenetic modifications are influenced by genetic variation and environmental exposures, and change with chronological age and between populations. Despite progress in identifying genetic, epigenetic, and environmental risk factors, the underlying mechanism of systemic sclerosis remains unclear. Since epigenetics provides the regulatory mechanism linking genetic and non-genetic factors to gene expression, understanding the role of epigenetic regulation in systemic sclerosis will elucidate how these factors interact to cause systemic sclerosis. Among the cell types under tight epigenetic control and susceptible to epigenetic dysregulation, immune cells are critically involved in early pathogenic events in the progression of fibrosis and systemic sclerosis. This review starts by summarizing the changes in DNA methylation, histone modification, and non-coding RNAs associated with systemic sclerosis. It then discusses the role of genetic, ethnic, age, and environmental effects on epigenetic regulation, with a focus on immune system dysregulation. Given the potential of epigenome editing technologies for cell reprogramming and as a therapeutic approach for durable gene regulation, this review concludes with a prospect on epigenetic editing. Although epigenomics in systemic sclerosis is in its infancy, future studies will help elucidate the regulatory mechanisms underpinning systemic sclerosis and inform the design of targeted epigenetic therapies to control its dysregulation.

scholarly journals Extracellular Vesicles in Cancer Metabolism: Implications for Cancer Diagnosis and Treatment

2021 ◽  
Vol 20 ◽  
pp. 153303382110378
Author(s):  
Qian Zhang ◽  
Xiangling Yang ◽  
Huanliang Liu
Keyword(s):  
Cancer Cells ◽  
Extracellular Vesicles ◽  
Cancer Diagnosis ◽  
Cancer Metabolism ◽  
Metabolic Reprogramming ◽  
Bioactive Molecules ◽  
Diagnosis And Treatment ◽  
Existing Problems ◽  
Non Coding Rnas

Metabolic reprogramming is one of the most common characteristics of cancer cells. The metabolic alterations of glucose, amino acids and lipids can support the aggressive phenotype of cancer cells. Exosomes, a kind of extracellular vesicles, participate in the intercellular communication through transferring bioactive molecules. Increasing evidence has demonstrated that enzymes, metabolites and non-coding RNAs in exosomes are responsible for the metabolic alteration of cancer cells. In this review, we summarize the past and recent findings of exosomes in altering cancer metabolism and elaborate on the role of the specific enzymes, metabolites and non-coding RNAs transferred by exosomes. Moreover, we give evidence of the role of exosomes in cancer diagnosis and treatment. Finally, we discuss the existing problems in the study and application of exosomes in cancer diagnosis and treatment.

scholarly journals Antigen-presenting cell-derived extracellular vesicles in accelerating atherosclerosis

2021 ◽  
Vol 8 (3) ◽  
pp. 4258-4265
Author(s):  
Alexander E Berezin ◽  
Alexander A Berezin
Keyword(s):  
Extracellular Vesicles ◽  
T Regulatory Cells ◽  
Bioactive Molecules ◽  
Atherosclerotic Plaques ◽  
Macrophage Phenotype ◽  
Non Coding Rnas ◽  
Microvascular Inflammation ◽  
Antigen Presenting ◽  
Endosomal System

Extracellular vesicles (EVs) are a population of heterogeneous particles that originate from the endosomal system or plasma membrane. Antigen-presenting cells (APCs) produce and release a broad spectrum of EVs involved in the pathogenesis of atherosclerosis. APC-derived EVs contain several bioactive molecules, such as non-coding RNAs, cytokines, chemokines, active proteins, immunomodulatory factors, and growth factors. The review focuses on the role of APC-derived EVs in regulating the transformation of macrophage phenotype, shaping foam cells, driving autophagy and/or inhibiting apoptosis of Th4+ cells, T regulatory cells, endothelial and smooth muscle cells (SMCs), as well as in facilitating oxidative stress in vasculature. APC-derived EVs act as triggers of angiogenesis, neovascularization and inflammation through their participation in microvascular inflammation, angiogenesis, development of atherosclerotic plaques, and modulation of their instability.

scholarly journals Targeting Inflammation after Myocardial Infarction: A Therapeutic Opportunity for Extracellular Vesicles?

2021 ◽  
Vol 22 (15) ◽  
pp. 7831
Author(s):  
Margarida Viola ◽  
Saskia C. A. de Jager ◽  
Joost P. G. Sluijter
Keyword(s):  
Myocardial Infarction ◽  
Immune System ◽  
Extracellular Vesicles ◽  
Cardiac Inflammation ◽  
Stem And Progenitor Cells ◽  
Therapeutic Opportunity ◽  
Strong Inflammatory Response ◽  
Non Coding Rnas ◽  
Dead Tissue

After myocardial infarction (MI), a strong inflammatory response takes place in the heart to remove the dead tissue resulting from ischemic injury. A growing body of evidence suggests that timely resolution of this inflammatory process may aid in the prevention of adverse cardiac remodeling and heart failure post-MI. The present challenge is to find a way to stimulate this process without interfering with the reparative role of the immune system. Extracellular vesicles (EVs) are natural membrane particles that are released by cells and carry different macromolecules, including proteins and non-coding RNAs. In recent years, EVs derived from various stem and progenitor cells have been demonstrated to possess regenerative properties. They can provide cardioprotection via several mechanisms of action, including immunomodulation. In this review, we summarize the role of the innate immune system in post-MI healing. We then discuss the mechanisms by which EVs modulate cardiac inflammation in preclinical models of myocardial injury through regulation of monocyte influx and macrophage function. Finally, we provide suggestions for further optimization of EV-based therapy to improve its potential for the treatment of MI.

scholarly journals Fluorogenic EXO-Probe Aptamers for Imaging and Tracking Exosomal RNAs

2021 ◽  
Author(s):  
Emily E Bonacquisti ◽  
Scott W Ferguson ◽  
Natalie E Jasiewicz ◽  
Jinli Wang ◽  
Adam D Brown ◽  
...  
Keyword(s):  
Cellular Communication ◽  
Multivesicular Bodies ◽  
Reporter System ◽  
Regulate Gene Expression ◽  
Fusion Construct ◽  
Versatile Tool ◽  
Non Coding Rnas ◽  
Exosomal Rnas ◽  
Epigenetic Processes

Small extracellular vesicles (sEVs), or exosomes, play important roles in physiological and pathological cellular communication. sEVs contain both short and long non-coding RNAs that regulate gene expression and epigenetic processes. Studying the intricacies of sEV function and RNA-based communication requires tools capable of labeling sEV RNA. Here we developed a novel genetically encodable reporter system for tracking sEV RNAs comprising an sEV-loading RNA sequence, termed the EXO-Code, fused to a fluorogenic RNA Mango aptamer for RNA imaging. This fusion construct allowed the visualization and tracking of RNA puncta and colocalization with markers of multivesicular bodies; imaging RNA puncta within sEVs; and quantification of sEVs. This technology represents a useful and versatile tool to interrogate the role of sEVs in cellular communication via RNA trafficking to sEVs, cellular sorting decisions, and sEV RNA cargo transfer to recipient cells.

The miRNA-kallikrein interaction: a mosaic of epigenetic regulation in cancer

2018 ◽  
Vol 399 (9) ◽  
pp. 973-982 ◽  
Author(s):  
Ashley Di Meo ◽  
Cong Wang ◽  
Yufeng Cheng ◽  
Eleftherios P. Diamandis ◽  
George M. Yousef
Keyword(s):  
Epigenetic Regulation ◽  
Serine Proteases ◽  
Untranslated Region ◽  
Regulate Gene Expression ◽  
Mrna Targets ◽  
Downstream Effectors ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation ◽  
Potential Cancer

AbstractThe kallikrein-related peptidases (KLKs) constitute a family of 15 highly conserved serine proteases with trypsin- and chymotrypsin-like activities. Dysregulated expression and/or aberrant activation of KLKs has been linked to various pathophysiological processes, including cancer. Many KLKs have been identified as potential cancer biomarkers. microRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression by pairing to the 3′ untranslated region (UTR) of complimentary mRNA targets. miRNAs are dysregulated in many cancers, including prostate, kidney and ovarian cancers. Several studies have shown that miRNAs are involved in the post-transcriptional regulation of KLKs. However, recent evidence suggests that miRNAs can also act as downstream effectors of KLKs. In this review, we provide an update on the epigenetic regulation of KLKs by miRNAs. We also present recent experimental evidence that supports the regulatory role of KLKs on miRNA networks. The potential diagnostic and therapeutic applications of miRNA-kallikrein interactions are also discussed.

scholarly journals The Role of Epigenetic Factors in Psoriasis

2021 ◽  
Vol 22 (17) ◽  
pp. 9294
Author(s):  
Klaudia Dopytalska ◽  
Piotr Ciechanowicz ◽  
Kacper Wiszniewski ◽  
Elżbieta Szymańska ◽  
Irena Walecka
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Significant Role ◽  
Disease Onset ◽  
Epigenetic Mechanisms ◽  
Epigenetic Factors ◽  
Individual Gene ◽  
Immune Mediated ◽  
Non Coding Rnas

Psoriasis is a chronic, systemic, immune-mediated disease with an incidence of approximately 2%. The pathogenesis of the disease is complex and not yet fully understood. Genetic factors play a significant role in the pathogenesis of the disease. In predisposed individuals, multiple trigger factors may contribute to disease onset and exacerbations of symptoms. Environmental factors (stress, infections, certain medications, nicotinism, alcohol, obesity) play a significant role in the pathogenesis of psoriasis. In addition, epigenetic mechanisms are considered result in modulation of individual gene expression and an increased likelihood of the disease. Studies highlight the significant role of epigenetic factors in the etiology and pathogenesis of psoriasis. Epigenetic mechanisms in psoriasis include DNA methylation, histone modifications and non-coding RNAs. Epigenetic mechanisms induce gene expression changes under the influence of chemical modifications of DNA and histones, which alter chromatin structure and activate transcription factors of selected genes, thus leading to translation of new mRNA without affecting the DNA sequence. Epigenetic factors can regulate gene expression at the transcriptional (via histone modification, DNA methylation) and posttranscriptional levels (via microRNAs and long non-coding RNAs). This study aims to present and discuss the different epigenetic mechanisms in psoriasis based on a review of the available literature.

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