Knockdown of exosome‑mediated lnc‑PVT1 alleviates lipopolysaccharide‑induced osteoarthritis progression by mediating the HMGB1/TLR4/NF‑κB 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-κB pathway through an mir-93-5p/HMGB1 axis. in summary, exosome-mediated PVT1 regulated lPS-induced osteoarthritis progression by modulating the HMGB1/Tlr4/nF-κB pathway via mir-93-5p, providing a new route for possible osteoarthritis treatment.

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

“…In addition, since the WOMAC index is highly correlated with the expression of lncRNA PCGEM1 in EVs, it is speculated that the severity of OA may be related to lncRNA PCGEM1, which may be a powerful indicator to distinguish early OA from late OA [ 22 ]. Studies have also found that compared with healthy people, LncRNA PVT1 in serum EVs of patients with osteoarthritis is significantly upregulated [ 23 ], while the level of miR-193b in plasma EVs of patients with OA is lower than that of healthy people [ 24 ].…”

Detection of SARS-CoV-2 infection by microRNA profiling of the upper respiratory tract

“…Studies using luciferase reporters carrying wild-type and altered IL-6 3'UTR con rm IL6 as a miR-142-3p target gene [7], while miR-142-3p acts in a dose-dependent manner to inhibits IL6 transcription in polymorphonuclear leukocytes stimulated with LPS [8]. miR-93-5p, also up-regulated in COVID-19 anterior nasal tissues, inhibits the production of IL-6, TNF and IL-1β in osteoarthritis and diabetic nephropathy models through regulation of high mobility group proteins HMGB1 and HMGA2, respectively [9,10]. IL-6 is one of the key mediators of viral cytokine storm and in ammation in patients with severe COVID-19 [11].…”

The Emerging Role of Non-Coding RNAs in Osteoarthritis

“…Mounting studies have revealed that multiple ncRNAs (lncRNAs, circRNAs, and miRNAs) have important roles in osteoarthritis through regulating the JAK/STAT and NF-κB cascades. As an illustration, lncRNA PVT1 could play an effective role in upregulating TLR4/NF-κB signaling cascade via modulating miR-93-5p/HMGB1 axis in osteoarthritis patients, therefore inducing osteoarthritis development ( 28 ). In addition, lncRNA-ATB overexpression could have a crucial part in downregulating the expression levels of iNOS, COX-2, IL-6 and TNF-α proteins.…”