Osteoclast microRNA profiling to capture the erosive factor in rheumatoid arthritis
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ABSTRACT:
PROVIDER: PRJNA863270 | ENA |
REPOSITORIES: ENA
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Project description:Background: In rheumatoid arthritis (RA), only a subset of patients develop an irreversible bone destruction. Our aim was to develop a microRNA (miR)-based osteoclast-related signature to predict erosiveness in RA. Results: We identified 5 miRs from PBMC-derived osteoclasts differentially expressed in RNASeq also in qPCR assessment. Conclusion: We found 5 miRNAs differentially refulated in erosive rheumtoid arhtritis compare to no erosve patient. This study could improve the current approach to identify RA subjects at risk of erosions, by adding biomarker signatures based on the profile of miRs in the osteoclasts.
2023-09-01 | GSE209982 | GEO
Project description:In rheumatoid arthritis (RA), only a subset of patients develop irreversible bone destruction. Our aim was to identify a microRNA (miR)-based osteoclast-related signature predictive of erosiveness in RA. Seventy-six adults with erosive (E) or nonerosive (NE) seropositive RA and 43 sex- and age-matched healthy controls were recruited. Twenty-five miRs from peripheral blood mononuclear cell (PBMC)-derived osteoclasts selected from RNA-Seq (discovery cohort) were assessed by qPCR (replication cohort), as were 33 target genes (direct targets or associated with regulated pathways). The top five miRs found differentially expressed in RA osteoclasts were either decreased (hsa-miR-34a-3p, 365b-3p, 374a-3p, and 511-3p [E versus NE]) or increased (hsa-miR-193b-3p [E versus controls]). In vitro, inhibition of miR-34a-3p had an impact on osteoclast bone resorption. An integrative network analysis of miRs and their targets highlighted correlations between mRNA and miR expression, both negative (CD38, CD80, SIRT1) and positive (MITF), and differential gene expression between NE versus E (GXYLT1, MITF) or versus controls (CD38, KLF4). Machine-learning models were used to evaluate the value of miRs and target genes, in combination with clinical data, to predict erosion. One model, including a set of miRs (predominantly 365b-3p) combined with rheumatoid factor titer, provided 70% accuracy (area under the curve [AUC] 0.66). Adding genes directly targeted or belonging to related pathways improved the predictive power of the model for the erosive phenotype (78% accuracy, AUC 0.85). This proof-of-concept study indicates that identification of RA subjects at risk of erosions may be improved by studying miR expression in PBMC-derived osteoclasts, suggesting novel approaches toward personalized treatment. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
| S-EPMC10443079 | biostudies-literature
Project description:Osteoclast differentiation is crucial for bone absorption and osteoclast is involved in bone destruction in rheumatoid arthritis. The aim of this study was to investigate the inhibitory effect of MJ2 on osteoclast differentiation and to elucidate its mechanism. Murine macrophage cell line, Raw 264.7 cells and collagen-induced arthritis mouse model were used for in vitro and in vivo study, respectively. MJ2-treated cells significantly inhibited osteoclast differentiation and decreased arthritic score. Surface proteins (SP) extracted from MJ2 also showed inhibitory effect on osteoclast differentiation by upregulating lipocalin 2 (lcn2) expression. Specifically, heat shock protein 60 (hsp60) in SP was revealed as an active component of MJ2. Hsp60 inhibited binding of receptor activator of nuclear factor-κB ligand (RANKL) to receptor activator of nuclear factor κB (RANK). In conclusion, MJ2 inhibited osteoclast formation and differentiation through lcn2 and RANKL-binding property and the effective component of MJ2 might be hsp60 present in surface layer.
2022-09-18 | GSE213113 | GEO
Project description:Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with localized bone involvement characterized by the presence of bone erosions. Evidence-based data suggest that under inflammatory conditions, classical monocytes are the main source of osteoclasts and might be involved in bone erosion pathophysiology. Here, we analyze the transcriptomic profile of classical monocytes in erosive and non-erosive rheumatoid arthritis patients in order to better understand their contribution to bone erosion. Thirty-nine premenopausal RA patients and 20 healthy age-matched women were recruited for this study. Classical monocytes were isolated from peripheral blood through negative selection. Sequencing library was constructed using the Quant-seq® 30 mRNA-Seq Library Prep Kit (Lexogen®) and sequenced using an Illumina Seq 2500 platform (Illumina®). Differential expression analysis was performed between patients and control groups. Therefore, gene sets analysis was performed to identify the enriched biological pathways. Results suggested that alterations in pathways related to the inflammatory process and impairment of bone formation have an important role in the pathophysiology of bone erosions in patients with rheumatoid arthritis.
2023-09-19 | E-MTAB-13361 | biostudies-arrayexpress
Project description:Immune cell dynamics in lymph nodes downstream of inflamed joints are associated with inflammatory-erosive arthritis in both tumor necrosis factor transgenic (TNF-Tg) mice and rheumatoid arthritis (RA) patients. In TNF-Tg mice, "Early" stages of arthritis are related to dramatic PLN "Expansion" with increases in joint-draining popliteal lymph node (PLN) volume and fluid flow, while CD21-high / CD23+ B-cells in inflamed nodes (Bin cells) accumulate in the PLN follicles. Onset of "Advanced" inflammatory-erosive arthritis is related to a PLN "Collapse" where fluid flow is reduced as Bin cells translocate from the PLN follicles into the sinuses and are thought to mechanically inhibit lymphatic drainage. Through single-cell RNA-sequencing, we aimed to evaluate changes in PLN immune cell populations during Early and Advanced arthritis to determine mechanisms mediating the Bin cell translocation and the relationship with arthritic progession in the afferent joints.
2023-08-14 | GSE211124 | GEO
Project description:To understand the pathogenic mechanisms of bone erosion in rheumatoid arthritis (RA), we investigated osteoclast-specific epigenetic programs, RANKL-responsive super-enhancers (SEs) and SE-associated enhancer RNAs (SE-eRNAs) in human osteoclasts. In this dataset, we sought for functional SE-eRNAs in RA patients' synovial monocytes.
2022-11-01 | GSE203357 | GEO
Project description:Background: Osteoclasts play a crucial role in the maintenance, repair, and remodeling of bones of the adult vertebral skeleton due to their bone resorption capability. Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are associated with increased activity of osteoclasts.
Objectives: Our study aimed to investigate the dynamic proteomic changes during osteoclast differentiation in healthy donors, in RA, and in PsA.
Methods: Healthy donors', RA, and PsA patients' blood samples were collected, monocytes were isolated and differentiated into osteoclasts in vitro using M-CSF and RANK-L treatment. Mass Spectrometry based proteomics were used to analyze proteins from cell lysates. The expression changes were analysed with Gene Set Enrichment Analysis (GSEA).
Results: The analysis of the proteomic changes revealed that during the differentiation of the human osteoclasts expression of the proteins involved in metabolic activity, secretory function and cell polarity is increased; by contrast signaling pathways involved in the immune functions are downregulated. Interestingly, the differences between cells of healthy donors and RA/PsA patients are most pronounced after the final steps of differentiation to osteoclasts. In addition both in RA and PsA the differentiation is characterized by decreased metabolic activity, associated with various immune pathway activities; furthermore by accelerated cytokine production in RA.
Conclusions: Our results shed light to the characteristic proteomic changes during human osteoclast differentiation and expression differences in RA and PsA, which reveal important pathophysiological insights in both diseases.
2022-03-16 | MSV000089073 | MassIVE
Project description:Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease of unknown etiology and pronounced inter-patient heterogeneity. To characterize RA at the molecular level and to uncover key pathomechanisms, we performed whole-genome gene expression analyses. Synovial tissues from rheumatoid arthritis patients were compared to those from osteoarthritis patients and to normal donors. Keywords: disease state analysis
2004-11-04 | GSE1919 | GEO
Project description:Determine the comprehensive miRNA expression profile in RNA extracted from whole blood samples from healthy controls (CTRL), individuals positive to CCP antibodies >25UI/ml (CCP+), early rheumatoid arthritis (ERA) and established rheumatoid arthritis (CRA) according to the ACR/EULAR 2010 classification criteria. Several miRNAs were overexpressed on ERA patients. We selected 5 miRNAs (miR-361-5p, miR-23a-3p, miR-223-3p, miR-4634 and miR-128-3p) for its quantification on a bigger group of subjects by RT-qPCR and the results showed good concordance with microarray expression data.
2019-06-13 | GSE115885 | GEO
Project description:Genome-wide DNA methylation level was studied to determine whether Rheumatoid arthritis patients (cases) has methylation differences comparing to normal controls in PBLs. We used Illumina HumanMethylation450 BeadChip array to determine the genome-wide DNA methylation difference in PBLs from Rheumatoid arthritis patients (cases) and normal controls Bisulphite converted DNA from the Rheumatoid arthritis patients (cases) and normal controls were hybridized to the Illumina Illumina HumanMethylation450 BeadChip arrays
2013-01-21 | E-GEOD-42861 | biostudies-arrayexpress