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Knockdown of exosome?mediated lnc?PVT1 alleviates lipopolysaccharide?induced osteoarthritis progression by mediating the HMGB1/TLR4/NF??B pathway via miR?93?5p.

ABSTRACT: Osteoarthritis is a chronic degenerative joint disease. Long non?coding RNA plasmacytoma variant translocation 1 (PVT1) is involved in the progression of osteoarthritis and exosomes serve a central role in intercellular communication. However, whether PVT1 can be mediated by exosomes in osteoarthritis has not been reported. Whole blood was drawn from osteoarthritis patients and healthy volunteers. Lipopolysaccharide (LPS) was used to stimulate human normal chondrocytes (C28/I2) to construct a cell damage model in vitro. Protein levels were examined via western blot analysis. eThe expression of PVT1, microRNA (miR)?93?5p and high mobility groupprotein B1 (HMGB1) was evaluated through reverse transcription?quantitative PCR. Cell viability and apoptosis were determined through CCK?8 or flow cytometric assay. Inflammatory cytokines were measured via ELISA. The relationship between PVT1 or HMGB1 and miR?93?5p was confirmed by dual?luciferase reporter assay. PVT1, HMGB1 and exosomal PVT1 were upregulated while miR?93?5p was downregulated in osteoarthritis patient serum and LPS?induced C28/I2 cells. Exosomes from osteoarthritis patient serum and LPS?treated C28/I2 cells increased PVT1 expression in C28/I2 cells. PVT1 depletion reversed the decrease of viability and the increase of apoptosis, inflammation responses and collagen degradation of C28/I2 cells induced by LPS. PVT1 regulated HMGB1 expression via sponging miR?93?5p. miR?93?5p inhibition abolished PVT1 silencing?mediated viability, apoptosis, inflammation responses and collagen degradation of LPS?stimulated C28/I2 cells. HMGB1 increase overturned miR?93?5p upregulation?mediated viability, apoptosis, inflammation responses and collagen degradation of LPS?stimulated C28/I2 cells. Furthermore, PVT1 modulated the Toll?like receptor 4/NF??B pathway through an miR?93?5p/HMGB1 axis. In summary, exosome?mediated PVT1 regulated LPS?induced osteoarthritis progression by modulating the HMGB1/TLR4/NF??B pathway via miR?93?5p, providing a new route for possible osteoarthritis treatment.

SUBMITTER: Meng Y

PROVIDER: S-EPMC7646997 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Knockdown of exosome‑mediated lnc‑PVT1 alleviates lipopolysaccharide‑induced osteoarthritis progression by mediating the HMGB1/TLR4/NF‑κB pathway via miR‑93‑5p.

Meng Yong Y Qiu Siqiang S Sun Long L Zuo Jinliang J

Molecular medicine reports 20201014 6

Osteoarthritis is a chronic degenerative joint disease. Long non‑coding RNA plasmacytoma variant translocation 1 (PVT1) is involved in the progression of osteoarthritis and exosomes serve a central role in intercellular communication. However, whether PVT1 can be mediated by exosomes in osteoarthritis has not been reported. Whole blood was drawn from osteoarthritis patients and healthy volunteers. Lipopolysaccharide (LPS) was used to stimulate human normal chondrocytes (C28/I2) to construct a ce ...[more]

PMID: 33174011

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Project description:Background: Atherosclerosis is a major cause of coronary artery disease (CAD), and CAD is one of the main causes leading to death in most countries. It has been reported that lncRNAs play important roles in the development of atherosclerosis; thus, we aimed to explore lncRNAs that are closely related to the occurrence and development of atherosclerosis. Methods: The data GSE113079 from the GEO database was used to explore the dysregulated lncRNAs in peripheral blood mononuclear cells (PBMCs) between 93 patients with CAD and 48 healthy controls. Next, RT-qPCR was performed to detect the level of lncRNAs in HUVEC cells and CCK-8 was performed to detect cell viability. Then, flow cytometry assays were used to determine the apoptosis of HUVEC. In addition, ELISA assay was used to measure the concentrations of triglyceride (TG), low density lipoprotein cholesterin (LDL-C), and high density lipoprotein cholesterol (HDL-C). Moreover, western blot assay was used to detect the expression of proteins. Results: lnc-KCNC3-3:1 was significantly upregulated in PBMCs of patients with CAD. In addition, oxidized low density lipoprotein (oxLDL) notably inhibited the proliferation and induced the apoptosis of HUVEC, while this phenomenon was notably reversed by lnc-KCNC3-3:1 knockdown. Moreover, oxLDL significantly promoted the migration of HUVECs, which was significantly restored by knockdown of lnc-KCNC3-3:1. Moreover, lnc-KCNC3-3:1 siRNA1 could reverse oxLDL-induced HUVEC growth inhibition, and lnc-KCNC3-3:1 silencing could inhibit the expressions of p-JAK1 and p-STAT3 in oxLDL-treated HUVECs. Animal study revealed that knockdown of lnc-KCNC3-3:1 alleviated the symptom of atherosclerosis, and it could inhibit the expressions of p-JAK1, p-STAT3 and p-Akt in tissues of atherosclerosis mice. Conclusion: Knockdown of lnc-KCNC3-3:1 alleviates the development of atherosclerosis via downregulation of JAK1/STAT3 signaling pathway. These data indicated that lnc-KCNC3-3:1 might serve as a potential target for the treatment of atherosclerosis.

Dataset Information

Knockdown of exosome?mediated lnc?PVT1 alleviates lipopolysaccharide?induced osteoarthritis progression by mediating the HMGB1/TLR4/NF??B pathway via miR?93?5p.

Publications

Knockdown of exosome‑mediated lnc‑PVT1 alleviates lipopolysaccharide‑induced osteoarthritis progression by mediating the HMGB1/TLR4/NF‑κB pathway via miR‑93‑5p.

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