Dataset Information

Moderate Mechanical Stimulation Protects Rats against Osteoarthritis through the Regulation of TRAIL via the NF-?B/NLRP3 Pathway.

ABSTRACT: The aim of this study was to examine exercise-related genes in articular cartilage identified through bioinformatics analysis to dissect the potential signaling pathway involved in mechanical stimulation in osteoarthritis (OA). To this end, we evaluated the GSE74898 dataset from the Gene Expression Omnibus database for exercise-related differentially expressed miRNAs (DE-miRNAs) using the R software package and predicted potential target genes for these miRNAs using miRTarBase. Functional annotation and pathway enrichment analysis were performed for these potential DE-miRNA targets. The effects of mechanical stimulation on the tumor necrosis factor-related apoptosis-induced ligand (TRAIL)/nuclear factor-kappa B (NF-?B)/nucleotide-binding and oligomerization domain-like receptor containing protein 3 (NLRP3) signaling pathway were evaluated in articular cartilage and chondrocytes. A total of 394 DE-miRNAs were identified (103 upregulated miRNAs; 291 downregulated miRNAs) in the cartilage of rats following treadmill exercise compared to the cartilage of unexercised control rats. Thus, mechanical stimulation could modulate the TRAIL/NF-?B/NLRP3 signaling pathway on OA. Histological and protein analysis demonstrated that moderate-intensity treadmill exercise could ameliorate OA through the downregulation of TRAIL. Furthermore, moderate cyclic tensile strain (CTS) could rescue chondrocytes from the effects of TRAIL via the inhibition of the nuclear translocation of NF-?B p65 and formation of NLRP3. Our findings indicate that moderate mechanical stimulation could ameliorate the degeneration of cartilage and chondrocyte damage through the inhibition of the TRAIL/NF-?B/NLRP3 pathway.

SUBMITTER: Yang Y

PROVIDER: S-EPMC7267856 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Moderate Mechanical Stimulation Protects Rats against Osteoarthritis through the Regulation of TRAIL via the NF-<i>κ</i>B/NLRP3 Pathway.

Yang Yue Y Wang Yang Y Kong Yawei Y Zhang Xiaoning X Zhang He H Feng Xinyuan X Wang Ziyuan Z Gao Peng P Yan Mingyue M Bai Lunhao L Li Feng F

Oxidative medicine and cellular longevity 20200523

The aim of this study was to examine exercise-related genes in articular cartilage identified through bioinformatics analysis to dissect the potential signaling pathway involved in mechanical stimulation in osteoarthritis (OA). To this end, we evaluated the GSE74898 dataset from the Gene Expression Omnibus database for exercise-related differentially expressed miRNAs (DE-miRNAs) using the R software package and predicted potential target genes for these miRNAs using miRTarBase. Functional annota ...[more]

PMID: 32566090

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Project description:Immunoglobulin A nephropathy (IgAN) is one of the most frequent kinds of primary glomerulonephritis characterized by IgA immune complexes deposition and glomerular proliferation. Zhen-wu-tang (ZWT), a well-known traditional Chinese formula has been reported to ameliorate various kidney diseases. However, its pharmacological mechanism remains unclear. Exosomes have been described in diverse renal diseases by mediating cellular communication but rarely in the IgAN. The purpose of the present study is to explore whether the underlying mechanisms of the effect of ZWT on IgAN is correlated to exosomes. Our results demonstrated that in human renal tubular epithelial cells (HK-2) stimulated by lipopolysaccharide, exosomes are obviously released after ZWT-containing serum treatment especially with 10% ZWT. In addition, once released, HK-2-derived exosomes were uptaked by human mesangial cells (HMC), which impeded the activation of NF-?B/NLRP3 signaling pathway to exert anti-inflammatory effects in a lipopolysaccharide induced proliferation model. Moreover, IgAN rat model was established by bovine serum albumin, CCL4 mixed solution and LPS. We found that 10% ZWT could significantly promote the release of exosomes from HK-2 and inhibit HMC proliferation to improve inflammation. Thus HK-2-derived exosomes treated with 10% ZWT (ZWT-EXO) were administered to the rats by tail vein injection. Our results showed that ZWT-EXO decreased the levels of 24 h proteinuria, urinary erythrocyte, IgA deposition in glomerulus and renal pathological injury which ameliorated the kidney damage. In addition, ZWT was able to dramatically promote secretion of exosomes in renal tissues while blocked NF-?B nuclear translocation as well as activation of NLRP3 inflammasome, leading to the inhibition of IL-1? and caspase-1. In conclusion, our study reveal that ZWT has protective effects on IgAN by regulating exosomes secretion to inhibit the activation of NF-?B/NLRP3 pathway, thereby attenuating the renal dysfunction. These findings may provide a new therapeutic target for the treatment of IgAN.

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Dataset Information

Moderate Mechanical Stimulation Protects Rats against Osteoarthritis through the Regulation of TRAIL via the NF-?B/NLRP3 Pathway.

Publications

Moderate Mechanical Stimulation Protects Rats against Osteoarthritis through the Regulation of TRAIL via the NF-<i>κ</i>B/NLRP3 Pathway.

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