Similar Datasets
Project description:Aging is a major risk factors for osteoarthritis (OA), and cartilage of the elder are more sensitive to mechanical loading stress. Recently, cartilage progenitor cells (CPCs) arose much interests due to its important role in maintaining cartilage homeostasis. However, the potential mechanism of increased sensitivity to mechanical stress in CPCs has not been elucidated. The aim of this study was to investigate the potential links between aging and age-related OA through establish CPCs replicative senescence model and fluid flow shear stress (FFSS) stimulated degeneration model. Small RNA and mRNA sequence were conducted to investigate miRNA-related mechanisms in this process. By gain-and-lost strategy we investigated the age-related miRNAs and their impacts on exacerbating the progression of biomechanical stimulated TMJ-OA. miR-708-5p was identified as age-related miRNA in CPCs, and TLR4 was identified as its direct target through luciferase report assay. Age-related miR-708-5p deficiency increased sensitivity of CPCs for exposure to FFSS by liberating TLR4 expression. Intra-articular delivery agomiR-708-5p alleviated TMJ osteoarthritic cartilage lesions in mice. In conclusion, age-related miR-708-5p deficiency increases the sensitivity to mechanical loading stress and promotes CPCs senescence like degeneration via TLR4.
2023-07-11 | GSE236978 | GEO
Project description:Aging is a major risk factors for osteoarthritis (OA), and cartilage of the elder are more sensitive to mechanical loading stress. Recently, cartilage progenitor cells (CPCs) arose much interests due to its important role in maintaining cartilage homeostasis. However, the potential mechanism of increased sensitivity to mechanical stress in CPCs has not been elucidated. The aim of this study was to investigate the potential links between aging and age-related OA through establish CPCs replicative senescence model and fluid flow shear stress (FFSS) stimulated degeneration model. Small RNA and mRNA sequence were conducted to investigate miRNA-related mechanisms in this process. By gain-and-lost strategy we investigated the age-related miRNAs and their impacts on exacerbating the progression of biomechanical stimulated TMJ-OA. miR-708-5p was identified as age-related miRNA in CPCs, and TLR4 was identified as its direct target through luciferase report assay. Age-related miR-708-5p deficiency increased sensitivity of CPCs for exposure to FFSS by liberating TLR4 expression. Intra-articular delivery agomiR-708-5p alleviated TMJ osteoarthritic cartilage lesions in mice. In conclusion, age-related miR-708-5p deficiency increases the sensitivity to mechanical loading stress and promotes CPCs senescence like degeneration via TLR4.
2023-07-11 | GSE236977 | GEO
Project description:Ageing related deficiency of miR-708-5p in osteoarthritic cartilage lesions
| PRJNA993237 | ENA
Project description:Ageing related deficiency of miR-708-5p in osteoarthritic cartilage lesions [miRNA]
| PRJNA993238 | ENA
Project description:Ageing related deficiency of miR-708-5p in osteoarthritic cartilage lesions [RNA]
| PRJNA993239 | ENA
Project description:BackgroundBone homeostasis is a tightly orchestrated process maintained by osteoblasts and osteoclasts, and a disruption of their steady-state equilibrium can lead to the occurrence of osteoporosis (OP).MethodsWe investigated the differential expression of micro (mi)RNAs in the bone tissues of a postmenopausal osteoporosis rat model induced by ovariectomy (OVX). Real-time PCR was used to verify the differentially expressed miRNAs in bone samples from OP patients and controls. The specific targets of two differentially expressed miRNAs in osteogenic or osteoclast differentiation were determined by bioinformatic prediction, and mRNA and protein detection.ResultsmiR-708-5p and miR-708-3p were highly expressed in the bone tissue of OVX rats and OP patients. miR-708-5p negatively regulated osteoblast differentiation in bone marrow mesenchymal stem cells by targeting SMAD specific E3 ubiquitin protein ligase 2, while miR-708-3p positively regulated osteoclast differentiation in bone marrow monocytes by targeting cerebellar degeneration associated protein 1 antisense RNA. miR-708-5p and miR-708-3p were shown to originate from the same precursor miRNA and to have a synergistic effect on the development of osteoporosis with different temporal and spatial patterns.ConclusionOur findings provide a referential theoretical basis and targets for the prevention and treatment of osteoporosis.
| S-EPMC7745577 | biostudies-literature
Project description:BACKGROUND:Duchenne (DMD) and Becker (BMD) muscular dystrophies are caused by mutations in the DMD gene coding for dystrophin, a protein being part of a large sarcolemmal protein scaffold that includes the neuronal nitric oxide synthase (nNOS). The nNOS was shown to play critical roles in a variety of muscle functions and alterations of its expression and location in dystrophic muscle fiber leads to an increase of the muscle fatigability. We previously revealed a decrease of nNOS expression in BMD patients all presenting a deletion of exons 45 to 55 in the DMD gene (BMDd45-55), impacting the nNOS binding site of dystrophin. Since several studies showed deregulation of microRNAs (miRNAs) in dystrophinopathies, we focused on miRNAs that could target nNOS in dystrophic context. METHODS:By a screening of 617 miRNAs in BMDd45-55 muscular biopsies using TLDA and an in silico study to determine which one could target nNOS, we selected four miRNAs. In order to select those that targeted a sequence of 3'UTR of NOS1, we performed luciferase gene reporter assay in HEK393T cells. Finally, expression of candidate miRNAs was modulated in control and DMD human myoblasts (DMDd45-52) to study their ability to target nNOS. RESULTS:TLDA assay and the in silico study allowed us to select four miRNAs overexpressed in muscle biopsies of BMDd45-55 compared to controls. Among them, only the overexpression of miR-31, miR-708, and miR-34c led to a decrease of luciferase activity in an NOS1-3'UTR-luciferase assay, confirming their interaction with the NOS1-3'UTR. The effect of these three miRNAs was investigated on control and DMDd45-52 myoblasts. First, we showed a decrease of nNOS expression when miR-708 or miR-34c were overexpressed in control myoblasts. We then confirmed that DMDd45-52 cells displayed an endogenous increased of miR-31, miR-708, and miR-34c and a decreased of nNOS expression, the same characteristics observed in BMDd45-55 biopsies. In DMDd45-52 cells, we demonstrated that the inhibition of miR-708 and miR-34c increased nNOS expression, confirming that both miRNAs can modulate nNOS expression in human myoblasts. CONCLUSION:These results strongly suggest that miR-708 and miR-34c, overexpressed in dystrophic context, are new actors involved in the regulation of nNOS expression in dystrophic muscle.
| S-EPMC5924477 | biostudies-literature
Project description:MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression post-transcriptionally. They are crucial for normal development and maintaining homeostasis. Researchers have discovered that dysregulated miRNA expression contributes to many pathological conditions, including cancer. miRNAs can augment or suppress tumorigenesis based on their expression and transcribed targetome in various cell types. In recent years, researchers have begun to identify miRNAs commonly dysregulated in cancer. One recently identified miRNA, miR-708-5p, has been shown to have profound roles in promoting or suppressing oncogenesis in a myriad of solid and hematological tumors. This review highlights the diverse, sometimes controversial findings reported for miR-708-5p in cancer, and the importance of further exploring this exciting miRNA.
| S-EPMC5642637 | biostudies-literature
Project description:IntroductionCartilage protein distribution and the changes that occur in cartilage ageing and disease are essential in understanding the process of cartilage ageing and age related diseases such as osteoarthritis. The aim of this study was to investigate the peptide profiles in ageing and osteoarthritic (OA) cartilage sections using matrix assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI).MethodsThe distribution of proteins in young, old and OA equine cartilage was compared following tryptic digestion of cartilage slices and MALDI-MSI undertaken with a MALDI SYNAPT™ HDMS system. Protein identification was undertaken using database searches following multivariate analysis. Peptide intensity differences between young, ageing and OA cartilage were imaged with Biomap software. Analysis of aggrecanase specific cleavage patterns of a crude cartilage proteoglycan extract were used to validate some of the differences in peptide intensity identified. Immunohistochemistry studies validated the differences in protein abundance.ResultsYoung, old and OA equine cartilage was discriminated based on their peptide signature using discriminant analysis. Proteins including aggrecan core protein, fibromodulin, and cartilage oligomeric matrix protein were identified and localised. Fibronectin peptides displayed a stronger intensity in OA cartilage. Age-specific protein markers for collectin-43 and cartilage oligomeric matrix protein were identified. In addition potential fibromodulin and biglycan peptides targeted for degradation in OA were detected.ConclusionsMALDI-MSI provided a novel platform to study cartilage ageing and disease enabling age and disease specific peptides in cartilage to be elucidated and spatially resolved.
| S-EPMC4095688 | biostudies-literature
Project description:MicroRNAs (miRNAs) are small non-coding RNA species that have been shown to have roles in multiple processes that occur in higher eukaryotes. They act by binding to specific sequences in the 3' untranslated region of their target genes and causing the transcripts to be degraded by the RNA-induced silencing complex (RISC). MicroRNAs have previously been reported to demonstrate altered expression in several aging phenotypes such as cellular senescence and age itself. Here, we have measured the expression levels of 521 small regulatory microRNAs (miRNAs) in spleen tissue from young and old animals of 6 mouse strains with different median strain lifespans by quantitative real-time PCR. Expression levels of 3 microRNAs were robustly associated with strain lifespan, after correction for multiple statistical testing (miR-203-3p [β-coefficient = -0.6447, p = 4.8 × 10-11], miR-664-3p [β-coefficient = 0.5552, p = 5.1 × 10-8] and miR-708-5p [β-coefficient = 0.4986, p = 1.6 × 10-6]). Pathway analysis of binding sites for these three microRNAs revealed enrichment of target genes involved in key aging and longevity pathways including mTOR, FOXO and MAPK, most of which also demonstrated associations with longevity. Our results suggests that miR-203-3p, miR-664-3p and miR-708-5p may be implicated in pathways determining lifespan in mammals.
| S-EPMC5356331 | biostudies-literature