scholarly journals The Emerging Role of MicroRNAs in Bone Diseases and Their Therapeutic Potential

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 211
Author(s):  
Luis Alberto Bravo Vázquez ◽  
Mariana Yunuen Moreno Becerril ◽  
Erick Octavio Mora Hernández ◽  
Gabriela García de León Carmona ◽  
María Emilia Aguirre Padilla ◽  
...  

MicroRNAs (miRNAs) are a class of small (20–24 nucleotides), highly conserved, non-coding RNA molecules whose main function is the post-transcriptional regulation of gene expression through sequence-specific manners, such as mRNA degradation or translational repression. Since these key regulatory molecules are implicated in several biological processes, their altered expression affects the preservation of cellular homeostasis and leads to the development of a wide range of pathologies. Over the last few years, relevant investigations have elucidated that miRNAs participate in different stages of bone growth and development. Moreover, the abnormal expression of these RNA molecules in bone cells and tissues has been significantly associated with the progression of numerous bone diseases, including osteoporosis, osteosarcoma, osteonecrosis and bone metastasis, among others. In fact, miRNAs regulate multiple pathological mechanisms, including altering either osteogenic or osteoblast differentiation, metastasis, osteosarcoma cell proliferation, and bone loss. Therefore, in this present review, aiming to impulse the research arena of the biological implications of miRNA transcriptome in bone diseases and to explore their potentiality as a theragnostic target, we summarize the recent findings associated with the clinical significance of miRNAs in these ailments.

Author(s):  
Dijie Li ◽  
Chaofei Yang ◽  
Chong Yin ◽  
Fan Zhao ◽  
Zhihao Chen ◽  
...  

Background: Bone is an important tissue and its normal function requires tight coordination of transcriptional networks and signaling pathways, and many of these networks/ pathways are dysregulated in pathological conditions affecting cartilage and bones. Long non-coding RNA (lncRNA) refers to a class of RNAs with a length of more than 200 nucleotides, lack of protein-coding potential, and exhibiting a wide range of biological functions. Although studies on lcnRNAs are still in their infancy, they have emerged as critical players in bone biology and bone diseases. The functions and exact mechanism of bone-related lncRNAs have not been fully classified yet. Objective: The objective of this article is to summarize the current literature on lncRNAs on the basis of their role in bone biology and diseases, focusing on their emerging molecular mechanism, pathological implications and therapeutic potential. Discussion: A number of lncRNAs have been identified and shown to play important roles in multiple bone cells and bone disease. The function and mechanism of bone-related lncRNA remain to be elucidated. Conclusion: At present, majority of knowledge is limited to cellular levels and less is known on how lncRNAs could potentially control the development and homeostasis of bone. In the present review, we highlight some lncRNAs in the field of bone biology and bone disease. We also delineate some lncRNAs that might have deep impacts on understanding bone diseases and providing new therapeutic strategies to treat these diseases.


2018 ◽  
Vol 159 (7) ◽  
pp. 245-251 ◽  
Author(s):  
Zoltán Nagy ◽  
Ábel Decmann ◽  
Pál Perge ◽  
Péter Igaz

Abstract: Adrenocortical tumours are quite prevalent. Most of these tumours are benign, hormonally inactive adrenocortical adenomas. Rare hormone-secreting adrenocortical adenomas are associated with severe clinical consequences, whereas the prognosis of the rare adrenocortical cancer is rather poor in its advanced stages. The pathogenesis of these tumours is only partly elucidated. MicroRNAs are small, non-coding RNA molecules that are pivotal in the regulation of several basic cell biological processes via the posttranscriptional regulation of gene expression. Their altered expression has been described in many tumours. Several tissue microRNAs, such as miR-483-5p, miR-503, miR-210, miR-335 and miR-195 were found to be differentially expressed among benign and malignant adrenocortical tumours, and these could also have pathogenic relevance. Due to their tissue specific and stable expression, microRNAs can be exploited in diagnostics as well. As the histological diagnosis of adrenocortical malignancy is difficult, microRNAs might be of help in the establishment of malignancy. Novel data show that microRNAs are secreted in various body fluids, projecting their applicability as biomarkers as part of liquid biopsy. In this review, we attempt to present a synopsis on the pathogenic relevance of microRNAs in adrenocortical tumours and their potential diagnostic applicability. Orv Hetil. 2018; 159(7): 245–251.


Biomics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 166-175
Author(s):  
Е.А. Зорин ◽  
О.А. Кулаева ◽  
В.А. Жуков

MicroRNAs are small non-coding RNA molecules that act as post-transcriptional regulators of gene expression due to rather strict complementarity to their mRNA and have a length of 20-24 nucleotides. Plant microRNAs control a wide range of physiological processes, including nutrition, growth, resistance reactions and interaction with other organisms, via modulation of the expression of transcription factors, stress-induced proteins, hormone biosynthesis enzymes, and other genes. Legumes are able to form mutualistic symbioses simultaneously with nitrogen-fixing bacteria and arbuscular mycorrhiza. Both the early and late stages of these symbiosis are regulated by complex genetic mechanisms. As it has become known in recent years, one of these mechanisms is the regulation of gene expression by microRNA. The study of microRNAs is carried out by various methods, but over the past decade, next-generation sequencing (NGS) technologies have become the most popular approach in this field. NGS is used to identify conservative and novel microRNAs in the genomes of various organisms (both model and non-model), as well as to study the functioning of microRNAs in various experimental conditions with the additional use of transcriptome and degradome sequencing data. The article describes the main stages of working with microRNA sequencing data: quality control of reads (with a list of programs required at this stage), identification of conservative and novel microRNAs using miRDeep2 tool, search for targets of identified microRNAs using PAREsnip2, functional annotation of targets and the use of statistical tests for the analysis of functional enrichment, which facilitates the interpretation of the data obtained and allows us to make assumptions about the biological consequences of the activity of identified microRNAs in the object under study. This information may be useful for researchers who deal with microRNAs in silico for the first time or want to save time and resources on searching and analyzing information about the tools needed to work with microRNA sequencing data.


Bone Research ◽  
2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Xing Yin ◽  
Chenchen Zhou ◽  
Jingtao Li ◽  
Renkai Liu ◽  
Bing Shi ◽  
...  

Abstract Autophagy is an evolutionarily conserved intracellular process, in which domestic cellular components are selectively digested for the recycling of nutrients and energy. This process is indispensable for cell homeostasis maintenance and stress responses. Both genetic and functional studies have demonstrated that multiple proteins involved in autophagic activities are critical to the survival, differentiation, and functioning of bone cells, including osteoblasts, osteocytes, and osteoclasts. Dysregulation at the level of autophagic activity consequently disturbs the balance between bone formation and bone resorption and mediates the onset and progression of multiple bone diseases, including osteoporosis. This review aims to introduce the topic of autophagy, summarize the understanding of its relevance in bone physiology, and discuss its role in the onset of osteoporosis and therapeutic potential.


2019 ◽  
Vol 65 (4) ◽  
Author(s):  
Joanna Bujak ◽  
Patrycja Kopytko ◽  
Małgorzata Lubecka ◽  
Katarzyna Sokołowska ◽  
Maciej Tarnowski

Angiogenesis is the process that leads to the formation of new blood vessels. Under physiological conditions it occurs, inter alia, during corpus luteum formation and in some stages of the menstrual cycle. However, angiogenesis plays an essential role in many pathological conditions, particularly cancer. New blood vessel formation provides cancer cells with oxygen and essential nutrients, which stimulates tumor growth and facilitates its metastasis. Increasing evidence indicates that angiogenesis is regulated by microRNAs (miRNAs), which are small non-coding RNA molecules of 19–25 nucleotides. The main function of miRNAs is post-transcriptional regulation of gene expression, which controls many key biological processes, including cell proliferation, differentiation and migration. Endothelial miRNAs, known as angiomiRs, are presumably involved in tumor development and angiogenesis through regulation of pro- and antiangiogenic factors. To date, the miRNAs that stimulate angiogenesis are: miR-9, miR-27a, miR-30d, miR0-130b, miR-139, miR-146a, miR-150, miR-155, miR-200c, miR-296 and miR-558. Conversely, miRNAs that inhibit angiogenesis are: miR-145, miR-519c, miR-22, miR-20a, miR-92, miR-7b, miR-221, miR-222, miR-328 and miR-101.


2021 ◽  
Vol 7 (3) ◽  
pp. 50
Author(s):  
Anastasia A. Sadova ◽  
Dmitry Y. Panteleev ◽  
Galina V. Pavlova

Ribosomal intergenic spacer (rIGS), located between the 45S rRNA coding arrays in humans, is a deep, unexplored source of small and long non-coding RNA molecules transcribed in certain conditions to help a cell generate a stress response, pass through a differentiation state or fine tune the functioning of the nucleolus as a ribosome biogenesis center of the cell. Many of the non-coding transcripts originating from the rIGS are not characterized to date. Here, we confirm the transcriptional activity of the region laying a 2 kb upstream of the rRNA promoter, and demonstrate its altered expression under transcriptional stress, induced by a wide range of known transcription inhibitors. We managed to show an increased variability of anti-sense transcripts in alpha-amanitin treated cells by applying the low-molecular RNA fraction extracted from agarose gel to PAGE-northern. Also, the fractioning of RNA by size using agarose gel slices occurred, being applicable for determining the sizes of target transcripts via RT-PCR.


2021 ◽  
Vol 1 (3) ◽  
pp. 403-423
Author(s):  
Elahe Soltani-Fard ◽  
Sina Taghvimi ◽  
Zahra Abedi Kichi ◽  
Christian Weber ◽  
Zahra Shabaninejad ◽  
...  

Non-coding RNAs (ncRNAs) are functional RNA molecules that comprise about 80% of both mammals and prokaryotes genomes. Recent studies have identified a large number of small regulatory RNAs in Escherichia coli and other bacteria. In prokaryotes, RNA regulators are a diverse group of molecules that modulate a wide range of physiological responses through a variety of mechanisms. Similar to eukaryotes, bacterial microRNAs are an important class of ncRNAs that play an important role in the development and secretion of proteins and in the regulation of gene expression. Similarly, riboswitches are cis-regulatory structured RNA elements capable of directly controlling the expression of downstream genes in response to small molecule ligands. As a result, riboswitches detect and respond to the availability of various metabolic changes within cells. The most extensive and most widely studied set of small RNA regulators act through base pairing with RNAs. These types of RNAs are vital for prokaryotic life, activating or suppressing important physiological processes by modifying transcription or translation. The majority of these small RNAs control responses to changes in environmental conditions. Finally, clustered regularly interspaced short palindromic repeat (CRISPR) RNAs, a newly discovered RNA regulator group, contains short regions of homology to bacteriophage and plasmid sequences that bacteria use to splice phage DNA as a defense mechanism. The detailed mechanism is still unknown but devoted to target homologous foreign DNAs. Here, we review the known mechanisms and roles of non-coding regulatory RNAs, with particular attention to riboswitches and their functions, briefly introducing translational applications of CRISPR RNAs in mammals.


2020 ◽  
Vol 7 ◽  
Author(s):  
Silvia Miretti ◽  
Cristina Lecchi ◽  
Fabrizio Ceciliani ◽  
Mario Baratta

MicroRNAs (miRNAs) are small and highly conserved non-coding RNA molecules that orchestrate a wide range of biological processes through the post-transcriptional regulation of gene expression. An intriguing aspect in identifying these molecules as biomarkers is derived from their role in cell-to-cell communication, their active secretion from cells into the extracellular environment, their high stability in body fluids, and their ease of collection. All these features confer on miRNAs the potential to become a non-invasive tool to score animal welfare. There is growing interest in the importance of miRNAs as biomarkers for assessing the welfare of livestock during metabolic, environmental, and management stress, particularly in ruminants, pigs, and poultry. This review provides an overview of the current knowledge regarding the potential use of tissue and/or circulating miRNAs as biomarkers for the assessment of the health and welfare status in these livestock species.


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
J. Guedes ◽  
A. L. C. Cardoso ◽  
M. C. Pedroso de Lima

MicroRNAs (miRNAs) are an abundant class of small noncoding RNA molecules that play an important role in the regulation of gene expression at the posttranscriptional level. Due to their ability to simultaneously modulate the fate of different genes, these molecules are particularly well suited to act as key regulators during immune cell differentiation and activation, and their dysfunction can contribute to pathological conditions associated with neuroinflammation. Recent studies have addressed the role of miRNAs in the differentiation of progenitor cells into microglia and in the activation process, aiming at clarifying the origin of adult microglia cells and the contribution of the central nervous system (CNS) environment to microglia phenotype, in health and disease. Altered expression of several miRNAs has been associated with Alzheimer’s disease, multiple sclerosis, and ischemic injury, hence strongly advocating the use of these small molecules as disease markers and new therapeutic targets. This review summarizes the recent advances in the field of miRNA-mediated regulation of microglia development and activation. We discuss the role of specific miRNAs in the maintenance and switching of microglia activation states and illustrate the potential of this class of nucleic acids both as biomarkers of inflammation and new therapeutic tools for the modulation of microglia behavior in the CNS.


2020 ◽  
Vol 27 (6) ◽  
pp. 838-853 ◽  
Author(s):  
Madalina Icriverzi ◽  
Valentina Dinca ◽  
Magdalena Moisei ◽  
Robert W. Evans ◽  
Mihaela Trif ◽  
...  

: Among the multiple properties exhibited by lactoferrin (Lf), its involvement in bone regeneration processes is of great interest at the present time. A series of in vitro and in vivo studies have revealed the ability of Lf to promote survival, proliferation and differentiation of osteoblast cells and to inhibit bone resorption mediated by osteoclasts. Although the mechanism underlying the action of Lf in bone cells is still not fully elucidated, it has been shown that its mode of action leading to the survival of osteoblasts is complemented by its mitogenic effect. Activation of several signalling pathways and gene expression, in an LRPdependent or independent manner, has been identified. Unlike the effects on osteoblasts, the action on osteoclasts is different, with Lf leading to a total arrest of osteoclastogenesis. : Due to the positive effect of Lf on osteoblasts, the potential use of Lf alone or in combination with different biologically active compounds in bone tissue regeneration and the treatment of bone diseases is of great interest. Since the bioavailability of Lf in vivo is poor, a nanotechnology- based strategy to improve the biological properties of Lf was developed. The investigated formulations include incorporation of Lf into collagen membranes, gelatin hydrogel, liposomes, loading onto nanofibers, porous microspheres, or coating onto silica/titan based implants. Lf has also been coupled with other biologically active compounds such as biomimetic hydroxyapatite, in order to improve the efficacy of biomaterials used in the regulation of bone homeostasis. : This review aims to provide an up-to-date review of research on the involvement of Lf in bone growth and healing and on its use as a potential therapeutic factor in bone tissue regeneration.


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