LncRNA, Important Player in Bone Development and Disease

2020 ◽  
Vol 20 (1) ◽  
pp. 50-66 ◽  
Author(s):  
Dijie Li ◽  
Chaofei Yang ◽  
Chong Yin ◽  
Fan Zhao ◽  
Zhihao Chen ◽  
...  
Keyword(s):  
Bone Disease ◽  
Bone Cells ◽  
Therapeutic Potential ◽  
Bone Development ◽  
Normal Function ◽  
Bone Diseases ◽  
Transcriptional Networks ◽  
Bone Biology ◽  
Protein Coding ◽  
Wide Range

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.

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 ◽  
...  
Keyword(s):  
Bone Growth ◽  
Bone Cells ◽  
Therapeutic Potential ◽  
Regulation Of Gene Expression ◽  
Bone Diseases ◽  
Osteosarcoma Cell ◽  
Main Function ◽  
Altered Expression ◽  
Rna Molecules ◽  
Wide Range

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.

scholarly journals Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Rinaldo Florencio-Silva ◽  
Gisela Rodrigues da Silva Sasso ◽  
Estela Sasso-Cerri ◽  
Manuel Jesus Simões ◽  
Paulo Sérgio Cerri
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Bone Tissue ◽  
Bone Remodeling ◽  
Bone Cells ◽  
Current Data ◽  
Bone Diseases ◽  
Bone Homeostasis ◽  
Bone Biology ◽  
Structure And Functions

Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local (e.g., growth factors and cytokines) and systemic (e.g., calcitonin and estrogens) factors that all together contribute for bone homeostasis. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells. For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts. Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology. It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue. In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling.

radiological features of the brittle bone diseases

2003 ◽  
Vol 5 (1) ◽  
pp. 39-45 ◽  
Author(s):  
c. r. paterson
Keyword(s):  
Osteogenesis Imperfecta ◽  
Bone Disease ◽  
Bone Diseases ◽  
X Rays ◽  
Accidental Injury ◽  
Radiological Features ◽  
Wide Range ◽  
Brittle Bone Disease ◽  
Non Accidental Injury ◽  
Temporary Brittle Bone Disease

this paper describes some radiological features of osteogenesis imperfecta and temporary brittle bone disease. both conditions cause fractures in early childhood that the parents cannot explain. they can underlie the finding of unsuspected fractures when x-rays are done for other reasons, including fractures of different ages. both can readily be confused with non-accidental injury.in these disorders any type of fracture can occur; no fracture pattern makes bone disease more or less likely. metaphyseal fractures, often regarded as specific for non-accidental injury, also have a wide range of other causes including several bone diseases. osteopenia cannot be reliably used in diagnosis, not least because it can be absent in some bone diseases such as osteogenesis imperfecta. wormian bones, if present in excess, are a valuable pointer to osteogenesis imperfecta but their absence does not eliminate this diagnosis.there is growing evidence for the identification of temporary brittle bone disease as a distinctive disorder with its own characteristic clinical and radiological findings.

scholarly journals Autophagy in bone homeostasis and the onset of osteoporosis

Bone Research ◽  
2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Xing Yin ◽  
Chenchen Zhou ◽  
Jingtao Li ◽  
Renkai Liu ◽  
Bing Shi ◽  
...  
Keyword(s):  
Stress Responses ◽  
Bone Cells ◽  
Therapeutic Potential ◽  
Bone Diseases ◽  
Bone Homeostasis ◽  
Functional Studies ◽  
Evolutionarily Conserved ◽  
Intracellular Process ◽  
Cellular Components ◽  
Bone Physiology

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.

scholarly journals The Roles of FoxO Transcription Factors in Regulation of Bone Cells Function

2020 ◽  
Vol 21 (3) ◽  
pp. 692 ◽  
Author(s):  
Xiaoli Ma ◽  
Peihong Su ◽  
Chong Yin ◽  
Xiao Lin ◽  
Xue Wang ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Bone Cells ◽  
Bone Development ◽  
Mammalian Species ◽  
Bone Diseases ◽  
Intercellular Signaling ◽  
New Therapeutic Approaches ◽  
Evolutionarily Conserved ◽  
Multiple Cell ◽  
Foxo Transcription Factors

Forkhead box class O family member proteins (FoxOs) are evolutionarily conserved transcription factors for their highly conserved DNA-binding domain. In mammalian species, all the four FoxO members, FoxO1, FoxO3, FoxO4, and FoxO6, are expressed in different organs. In bone, the first three members are extensively expressed and more studied. Bone development, remodeling, and homeostasis are all regulated by multiple cell lineages, including osteoprogenitor cells, chondrocytes, osteoblasts, osteocytes, osteoclast progenitors, osteoclasts, and the intercellular signaling among these bone cells. The disordered FoxOs function in these bone cells contribute to osteoarthritis, osteoporosis, or other bone diseases. Here, we review the current literature of FoxOs for their roles in bone cells, focusing on helping researchers to develop new therapeutic approaches and prevent or treat the related bone diseases.

scholarly journals Role of miR-140 in embryonic bone development and cancer

2015 ◽  
Vol 129 (10) ◽  
pp. 863-873 ◽  
Author(s):  
Darrell Green ◽  
Tamas Dalmay ◽  
William D. Fraser
Keyword(s):  
Cancer Biology ◽  
Bone Cells ◽  
Bone Development ◽  
Fine Tuning ◽  
Bone Biology ◽  
Development Activity ◽  
Rna Molecules ◽  
Molecular Events ◽  
Embryonic Bone

Bone is increasingly viewed as an endocrine organ with key biological functions. The skeleton produces hormones and cytokines, such as FGF23 and osteocalcin, which regulate an extensive list of homoeostatic functions. Some of these functions include glucose metabolism, male fertility, blood cell production and calcium/phosphate metabolism. Many of the genes regulating these functions are specific to bone cells. Some of these genes can be wrongly expressed by other malfunctioning cells, driving the generation of disease. The miRNAs are a class of non-coding RNA molecules that are powerful regulators of gene expression by suppressing and fine-tuning target mRNAs. Expression of one such miRNA, miR-140, is ubiquitous in chondrocyte cells during embryonic bone development. Activity in cells found in the adult breast, colon and lung tissue can silence genes required for tumour suppression. The realization that the same miRNA can be both normal and detrimental, depending on the cell, tissue and time point, provides a captivating twist to the study of whole-organism functional genomics. With the recent interest in miRNAs in bone biology and RNA-based therapeutics on the horizon, we present a review on the role of miR-140 in the molecular events that govern bone formation in the embryo. Cellular pathways involving miR-140 may be reactivated or inhibited when treating skeletal injury or disorder in adulthood. These pathways may also provide a novel model system when studying cancer biology of other cells and tissues.

Lactoferrin in Bone Tissue Regeneration

2020 ◽  
Vol 27 (6) ◽  
pp. 838-853 ◽  
Author(s):  
Madalina Icriverzi ◽  
Valentina Dinca ◽  
Magdalena Moisei ◽  
Robert W. Evans ◽  
Mihaela Trif ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Tissue Regeneration ◽  
Bone Cells ◽  
Bone Diseases ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Bone Tissue Regeneration ◽  
Bone Homeostasis ◽  
Active Compounds

: 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.

Isoform-Selective PI3K Inhibitors for Various Diseases

2020 ◽  
Vol 20 (12) ◽  
pp. 1074-1092 ◽  
Author(s):  
Rammohan R.Y. Bheemanaboina
Keyword(s):  
Intracellular Signaling ◽  
Kinase Inhibitors ◽  
Therapeutic Potential ◽  
Type I ◽  
Selective Inhibitors ◽  
Pi3k Inhibitors ◽  
Wide Range ◽  
Lipid Kinases ◽  
Isoform Selectivity

Phosphoinositide 3-kinases (PI3Ks) are a family of ubiquitously distributed lipid kinases that control a wide variety of intracellular signaling pathways. Over the years, PI3K has emerged as an attractive target for the development of novel pharmaceuticals to treat cancer and various other diseases. In the last five years, four of the PI3K inhibitors viz. Idelalisib, Copanlisib, Duvelisib, and Alpelisib were approved by the FDA for the treatment of different types of cancer and several other PI3K inhibitors are currently under active clinical development. So far clinical candidates are non-selective kinase inhibitors with various off-target liabilities due to cross-reactivities. Hence, there is a need for the discovery of isoform-selective inhibitors with improved efficacy and fewer side-effects. The development of isoform-selective inhibitors is essential to reveal the unique functions of each isoform and its corresponding therapeutic potential. Although the clinical effect and relative benefit of pan and isoformselective inhibition will ultimately be determined, with the development of drug resistance and the demand for next-generation inhibitors, it will continue to be of great significance to understand the potential mechanism of isoform-selectivity. Because of the important role of type I PI3K family members in various pathophysiological processes, isoform-selective PI3K inhibitors may ultimately have considerable efficacy in a wide range of human diseases. This review summarizes the progress of isoformselective PI3K inhibitors in preclinical and early clinical studies for anticancer and other various diseases.

scholarly journals Bioactive potential of natural biomaterials: identification, retention and assessment of biological properties

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Kieran Joyce ◽  
Georgina Targa Fabra ◽  
Yagmur Bozkurt ◽  
Abhay Pandit
Keyword(s):  
Tissue Engineering ◽  
Therapeutic Potential ◽  
Biological Properties ◽  
Biological Assessment ◽  
Cross Linking ◽  
Natural Polymers ◽  
Drug Delivery Device ◽  
Biomedical Device ◽  
Wide Range ◽  
Bioactive Potential

AbstractBiomaterials have had an increasingly important role in recent decades, in biomedical device design and the development of tissue engineering solutions for cell delivery, drug delivery, device integration, tissue replacement, and more. There is an increasing trend in tissue engineering to use natural substrates, such as macromolecules native to plants and animals to improve the biocompatibility and biodegradability of delivered materials. At the same time, these materials have favourable mechanical properties and often considered to be biologically inert. More importantly, these macromolecules possess innate functions and properties due to their unique chemical composition and structure, which increase their bioactivity and therapeutic potential in a wide range of applications. While much focus has been on integrating these materials into these devices via a spectrum of cross-linking mechanisms, little attention is drawn to residual bioactivity that is often hampered during isolation, purification, and production processes. Herein, we discuss methods of initial material characterisation to determine innate bioactivity, means of material processing including cross-linking, decellularisation, and purification techniques and finally, a biological assessment of retained bioactivity of a final product. This review aims to address considerations for biomaterials design from natural polymers, through the optimisation and preservation of bioactive components that maximise the inherent bioactive potency of the substrate to promote tissue regeneration.

scholarly journals Non-Coding RNAs in the Transcriptional Network That Differentiates Skeletal Muscles of Sedentary from Long-Term Endurance- and Resistance-Trained Elderly

2021 ◽  
Vol 22 (4) ◽  
pp. 1539
Author(s):  
Paola De Sanctis ◽  
Giuseppe Filardo ◽  
Provvidenza Maria Abruzzo ◽  
Annalisa Astolfi ◽  
Alessandra Bolotta ◽  
...  
Keyword(s):  
Exercise Training ◽  
High Intensity ◽  
Vastus Lateralis ◽  
Mammalian Target Of Rapamycin ◽  
Differentially Expressed ◽  
Transcriptional Networks ◽  
Vastus Lateralis Muscle ◽  
Age Related ◽  
Wide Range ◽  
Non Coding Rnas

In a previous study, the whole transcriptome of the vastus lateralis muscle from sedentary elderly and from age-matched athletes with an exceptional record of high-intensity, life-long exercise training was compared—the two groups representing the two extremes on a physical activity scale. Exercise training enabled the skeletal muscle to counteract age-related sarcopenia by inducing a wide range of adaptations, sustained by the expression of protein-coding genes involved in energy handling, proteostasis, cytoskeletal organization, inflammation control, and cellular senescence. Building on the previous study, we examined here the network of non-coding RNAs participating in the orchestration of gene expression and identified differentially expressed micro- and long-non-coding RNAs and some of their possible targets and roles. Unsupervised hierarchical clustering analyses of all non-coding RNAs were able to discriminate between sedentary and trained individuals, regardless of the exercise typology. Validated targets of differentially expressed miRNA were grouped by KEGG analysis, which pointed to functional areas involved in cell cycle, cytoskeletal control, longevity, and many signaling pathways, including AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), which had been shown to be pivotal in the modulation of the effects of high-intensity, life-long exercise training. The analysis of differentially expressed long-non-coding RNAs identified transcriptional networks, involving lncRNAs, miRNAs and mRNAs, affecting processes in line with the beneficial role of exercise training.

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