Systems analysis of miR-199a/b-5p and multiple miR-199a/b-5p targets during chondrogenesis.

Changes in chondrocyte gene expression can contribute to the development of osteoarthritis (OA), and so recognition of the regulative processes during chondrogenesis can lead to a better understanding of OA. microRNAs (miRNAs) are key regulators of gene expression in chondrocytes/OA, and we have used a combined experimental, bioinformatic, and systems biology approach to explore the multiple miRNA-mRNA interactions that regulate chondrogenesis. A longitudinal chondrogenesis bioinformatic analysis identified paralogues miR-199a-5p and miR-199b-5p as pro-chondrogenic regulators.

Epigenetic mechanisms of osteoarthritis risk in human skeletal development.

The epigenome, including the methylation of cytosine bases at CG dinucleotides, is intrinsically linked to transcriptional regulation. The tight regulation of gene expression during skeletal development is essential, with ~1/500 individuals born with skeletal abnormalities. Furthermore, increasing evidence is emerging to link age-associated complex genetic musculoskeletal diseases, including osteoarthritis (OA), to developmental factors including joint shape.

DNA methylation analysis identifies key transcription factors involved in mesenchymal stem cell osteogenic differentiation.

Background: Knowledge about regulating transcription factors (TFs) for osteoblastogenesis from mesenchymal stem cells (MSCs) is limited. Therefore, we investigated the relationship between genomic regions subject to DNA-methylation changes during osteoblastogenesis and the TFs known to directly interact with these regulatory regions.

Results: The genome-wide DNA-methylation signature of MSCs differentiated to osteoblasts and adipocytes was determined using the Illumina HumanMethylation450 BeadChip array.

Taxonomic assessment of two wild house mouse subspecies using whole-genome sequencing.

The house mouse species complex (Mus musculus) is comprised of three primary subspecies. A large number of secondary subspecies have also been suggested on the basis of divergent morphology and molecular variation at limited numbers of markers. While the phylogenetic relationships among the primary M.

HDAC6 regulates NF-κB signalling to control chondrocyte IL-1-induced MMP and inflammatory gene expression.

Elevated pro-inflammatory signalling coupled with catabolic metalloproteinase expression is a common feature of arthritis, leading to cartilage damage, deterioration of the joint architecture and the associated pain and immobility. Countering these processes, histone deacetylase inhibitors (HDACi) have been shown to suppress matrix metalloproteinase (MMP) expression, block cytokine-induced signalling and reduce the cartilage degradation in animal models of the arthritis. In order to establish which specific HDACs account for these chondro-protective effects an HDAC1-11 RNAi screen was performed.

Increased serum miR-193a-5p during non-alcoholic fatty liver disease progression: Diagnostic and mechanistic relevance.

Background & Aims: Serum microRNA (miRNA) levels are known to change in non-alcoholic fatty liver disease (NAFLD) and may serve as useful biomarkers. This study aimed to profile miRNAs comprehensively at all NAFLD stages.

Methods: We profiled 2,083 serum miRNAs in a discovery cohort (183 cases with NAFLD representing the complete NAFLD spectrum and 10 population controls).

Osteoarthritis year in review: genetics, genomics, epigenetics.

Objective: In this review, we have highlighted the advances over the past year in genetics, genomics and epigenetics in the field of osteoarthritis (OA).

Methods: A literature search of PubMed was performed using the criteria: "osteoarthritis" and one of the following terms "genetic(s), genomic(s), epigenetic(s), polymorphism, noncoding ribonucleic acid (RNA), microRNA, long noncoding RNA, lncRNA, circular RNA, RNA sequencing (RNA-seq), single cell sequencing, transcriptomics, or deoxyribonucleic acid (DNA) methylation between April 01, 2020 and April 30, 2021.

Results: In total we identified 765 unique publications, which eventually reduced to 380 of relevance to the field as judged by two assessors.

Simultaneous neutron powder diffraction and microwave characterisation at elevated temperatures.

The use of simultaneous neutron powder diffraction (NPD) and microwave characterisation can provide more information than the use of either technique individually; for example, it enables the differentiation of physisorbed and metal-coordinated species. Many possible experiments using these combined techniques can benefit from the addition of a heat source for sample heating, such as real-time measurements of solvent removal, or chemical and catalytic reactions. This paper documents the design of equipment to conduct simultaneous NPD and 2.

Increased hippocampal excitability in miR-324-null mice.

MicroRNAs are non-coding RNAs that act to downregulate the expression of target genes by translational repression and degradation of messenger RNA molecules. Individual microRNAs have the ability to specifically target a wide array of gene transcripts, therefore allowing each microRNA to play key roles in multiple biological pathways. miR-324 is a microRNA predicted to target thousands of RNA transcripts and is expressed far more highly in the brain than in any other tissue, suggesting that it may play a role in one or multiple neurological pathways.

The role of microRNA-3085 in chondrocyte function.

MicroRNAs have been shown to play a role in cartilage development, homeostasis and breakdown during osteoarthritis. We previously identified miR-3085 in humans as a chondrocyte-selective microRNA, however it could not be detected by Northern blot. The aim of the current study was to prove that miR-3085 is a microRNA and to investigate the function of miR-3085 in signaling pathways relevant to cartilage homeostasis and osteoarthritis.

OATargets: a knowledge base of genes associated with osteoarthritis joint damage in animals.

Objectives: To collate the genes experimentally modulated in animal models of osteoarthritis (OA) and compare these data with OA transcriptomics data to identify potential therapeutic targets.

Methods: PubMed searches were conducted to identify publications describing gene modulations in animal models. Analysed gene expression data were retrieved from the SkeletalVis database of analysed skeletal microarray and RNA-Seq expression data.

Regulation of microRNA-221, -222, -21 and -27 in articular cartilage subjected to abnormal compressive forces.

Key Points: microRNAs (miRs) are small non-coding molecules that regulate post-transcriptional target gene expression. miRs are involved in regulating cellular activities in response to mechanical loading in all physiological systems, although it is largely unknown whether this response differs with increasing magnitudes of load. miR-221, miR-222, miR-21-5p and miR-27a-5p were significantly increased in ex vivo cartilage explants subjected to increasing load magnitude and in in vivo joint cartilage exposed to abnormal loading.

Dynamic chromatin accessibility landscape changes following interleukin-1 stimulation.

Dynamic modifications of chromatin allow rapid access of the gene regulatory machinery to condensed genomic regions facilitating subsequent gene expression. Inflammatory cytokine stimulation of cells can cause rapid gene expression changes through direct signalling pathway-mediated transcription factor activation and regulatory element binding. Here we used the Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) to assess regions of the genome that are differentially accessible following treatment of cells with interleukin-1 (IL-1).

Comparative Molecular Life History of Spontaneous Canine and Human Gliomas.

Sporadic gliomas in companion dogs provide a window on the interaction between tumorigenic mechanisms and host environment. We compared the molecular profiles of canine gliomas with those of human pediatric and adult gliomas to characterize evolutionarily conserved mammalian mutational processes in gliomagenesis. Employing whole-genome, exome, transcriptome, and methylation sequencing of 83 canine gliomas, we found alterations shared between canine and human gliomas such as the receptor tyrosine kinases, TP53 and cell-cycle pathways, and IDH1 R132.

Osteoarthritis year in review 2019: genetics, genomics and epigenetics.

Although osteoarthritis (OA) aetiology is complex, genetic, genomic and epigenetic studies published within the last decade have advanced our understanding of the molecular processes underlying this common musculoskeletal disease. The purpose of this narrative review is to highlight the key research articles within the OA genetics, genomics and epigenetics fields that were published between April 2018 and April 2019. The review focuses on the identification of new OA genetic risk loci, genomics techniques that have been used for the first time in human cartilage and new publicly available databases, and datasets that will aid OA functional studies.

A novel dual mode X-band EPR resonator for rapid in situ microwave heating.

A unique dual mode X-band Continuous Wave (CW) EPR resonator designed for simultaneous EPR measurement and rapid microwave (MW) induced sample heating is described. Chemical reactions subjected to a flow of energy and matter can be perturbed away from the thermodynamic equilibrium by imposing a rapid shock or physical change to the system. Depending on the magnitude of the perturbation, these changes can dictate the subsequent evolution of the entire system, allowing for instance to populate non-equilibrium reactive intermediate states.

Kinetics Analysis of Circulating MicroRNAs Unveils Markers of Failed Myocardial Reperfusion.

Background: Failed myocardial reperfusion occurs in approximately 50% of patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI). It manifests as microvascular obstruction (MVO) on cardiac magnetic resonance (CMR) imaging. Although prognostically important, MVO is not routinely screened for.

The function of microRNAs in cartilage and osteoarthritis.

MicroRNAs are small double-stranded RNAs, which negatively regulate gene expression and have been shown to have key roles in both chondrocyte development and cartilage homeostasis with age. Deletion of all microRNAs in chondrocytes leads to skeletal growth defects in mice, whilst deletion of specific microRNAs, e.g.