Knockdown MiR-302b Alleviates LPS-Induced Injury by Targeting Smad3 in C28/I2 Chondrocytic Cells

Wang, Yueshu; Yu, Tao; Jin, Hui; Zhao, Cheng; Wang, Yang

doi:10.1159/000487165

Cited by 14 publications

(7 citation statements)

References 37 publications

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“…miRNAs have been confirmed as vital biomarkers in a number of diseases and regulate protein expression at the post-transcriptional level. miR-302b overexpression was confirmed to enhance the effects of LPS on apoptosis, inflammation and cell viability (46). In the present study, the miR-302b levels were elevated in the LPS-stimulated PdLScs and were downregulated by TMP in a concentration-dependent manner.…”

Section: Discussionsupporting

confidence: 71%

Tetramethylpyrazine reduces inflammation levels and the apoptosis of LPS‑stimulated human periodontal ligament cells via the downregulation of miR‑302b

Duan

et al. 2020

Int J Mol Med

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Periodontitis is the main cause of tooth or tissue loss. Human periodontal ligament stem cells (hPdLScs), which have high proliferative, self-renewal and multi-differentiation abilities, are vital for the restoration of periodontitis-induced injuries. The anti-inflammatory and anti-apoptotic agent, tetramethylpyrazine (TMP), is a promising agent used for the protection of PdLScs from apoptosis and inflammation induced by periodontitis. The aim of the present study was to investigate the effects of TMP on lipopolysaccharide (LPS)-stimulated hPdLScs. LPS-stimulated hPdLScs were established as the cell model. ccK-8 assay was performed to evaluate cell viability, western blot analysis was performed to measure protein expression and flow cytometry was performed to detect cell apoptosis levels. detection kits were used to evaluate the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6. Reverse transcription-quantitative PcR analysis was performed to detect gene expression. TMP alleviated the effects of LPS on cell viability, inflammation levels and cell apoptosis. TMP downregulated microRNA (miR)-302b levels in LPS-stimulated cells. Transfection with miR-302b mimic reversed the anti-inflammatory and anti-apoptotic effects of TMP on LPS-stimulated cells. TMP reduced inflammation and the apoptosis of LPS-stimulated human periodontal ligament cells via the downregulation of miR-302b. The anti-inflammatory and anti-apoptotic effects exerted by TMP render it a promising agent for the protection of PdLScs from injuries induced by periodontitis. The findings of the present study may aid in the development of a novel strategy for the treatment of periodontitis and may pave the way for further research.

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Section: Discussionsupporting

confidence: 71%

Tetramethylpyrazine reduces inflammation levels and the apoptosis of LPS‑stimulated human periodontal ligament cells via the downregulation of miR‑302b

Duan

et al. 2020

Int J Mol Med

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“…Notch1 positively regulates angiogenesis [51], while Notch2 negatively regulates cell proliferation [52] and angiogenesis [53]. In the initial stage of angiogenesis, inhibition of Notch 2 promotes vascular endothelial cell proliferation, while activation of Notch 2 reduces endothelial cell responses to VEGF [54, 55]. In the present study, Notch2 expression was mediated by miR-21a-3p.…”

Section: Discussionmentioning

confidence: 65%

The regulatory effect of microRNA-21a-3p on the promotion of telocyte angiogenesis mediated by PI3K (p110α)/AKT/mTOR in LPS induced mice ARDS

et al. 2019

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BackgroundTelocytes (TCs) are newly identified interstitial cells that participate in tissue protection and repair. The present study investigated the mechanisms underlying the protective effect of TCs in a mouse model of respiratory distress.MethodsThe mouse model of acute respiratory distress syndrome (ARDS) was established by intratracheal instillation of lipopolysaccharide (LPS). After instillation of TCs culture medium, lung injury was assessed, and angiogenesis markers, including CD31 and endothelial nitric oxide synthase (eNOS), were detected by immunofluorescence. Bioinformatics analysis was used to screen significantly differentially expressed microRNAs (miRNAs) in cultured TCs stimulated with LPS, and the regulation of downstream angiogenesis genes by these miRNAs was analysed and verified. PI3K subunits and pathways were evaluated by using a PI3K p110α inhibitor to study the involved mechanisms.ResultsIn ARDS mice, instillation of TCs culture medium ameliorated LPS-induced inflammation and lung injury and increased the protein levels of CD31 and eNOS in the injured lungs. A total of 7 miRNAs and 1899 mRNAs were differentially regulated in TCs stimulated with LPS. Functional prediction analysis showed that the differentially expressed mRNAs were enriched in angiogenesis-related processes, which were highly correlated with miR-21a-3p. Culture medium from TCs with miR-21a-3p inhibition failed to promote angiogenesis in mouse models of LPS-induced ARDS. In cultured TCs, LPS stimulation upregulated the expression of miR-21a-3p, which further targeted the transcription factor E2F8 and decreased Notch2 protein expression. TCs culture medium enhanced hemangioendothelioma endothelial cells (EOMA cells) proliferation, which was blocked by the miR-21a-3p inhibitor. The PI3K p110α inhibitor decreased vascular endothelial growth factor levels in LPS-stimulated TCs and reversed the enhancing effect of TCs culture medium on EOMA cells proliferation.ConclusionsTCs exerted protective effects under inflammatory conditions by promoting angiogenesis via miR-21a-3p. The PI3K p110α subunit and transcriptional factor E2F8 could be involved in this process.

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“…cells. Apoptosis and inflammation serve notable roles in OA development (28). Based on the aforementioned results, the effects of LINC00473 on cell injury in OA were investigated.…”

Section: Linc00473 Knockdown Reduces Chondrocyte Apoptosis and The Inflammatory Response In Il-1β-treated C28/i2mentioning

confidence: 99%

LINC00473 exacerbates osteoarthritis development by promoting chondrocyte apoptosis and proinflammatory cytokine production through the miR‑424‑5p/LY6E axis

et al. 2021

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Osteoarthritis (OA) is a common degenerative joint disease that has been identified as one of the major health burdens in aging individuals. Long non-coding RNAs (lncRNAs) participate in the development of diverse diseases, including OA. Among them, lncRNA long intergenic non-protein coding RNA 473 (LINC00473) is one of the few upregulated lncRNAs. The present study aimed to explore the role of LINC00473 and its regulatory mechanism in OA development. Flow cytometry analyses and ELISA were carried out to detect chondrocyte apoptosis and the concentration of proinflammatory cytokines, respectively. The results suggested that LINC00473 knockdown significantly reduced chondrocyte apoptosis and the production of proinflammatory cytokines in IL-1β-stimulated C28/I2 cells compared with transfection with small interfering RNA-negative control (si-NC). Western blot analyses were performed to examine protein levels of apoptotic markers (caspase-3, Bax and Bcl-2) in C28/I2 cells. Subsequently, an OA rat model was established to explore the role of LINC00473 in vivo. The results indicated that, compared with the OA + adeno-associated virus si-NC group, LINC00473 knockdown significantly suppressed the degradation of chondrocyte extracellular matrix and the production of proinflammatory cytokines in OA model rats. Furthermore, bioinformatics analysis, luciferase reporter and RNA immunoprecipitation assays indicated that LINC00473 served as a microRNA (miR)-424-5p sponge in C28/I2 cells, and that lymphocyte antigen 6 locus E (LY6E) was the downstream target. In addition, the inhibitory effects of LINC00473 knockdown on chondrocyte apoptosis and the inflammatory response could be reversed by LY6E overexpression in IL-1β-stimulated C28/I2 cells. In summary, the findings indicated that LINC00473 contributed to OA progression by modulating the miR-424-5p/LY6E axis, which may serve as a potential therapeutic strategy for patients with OA.

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Knockdown MiR-302b Alleviates LPS-Induced Injury by Targeting Smad3 in C28/I2 Chondrocytic Cells

Cited by 14 publications

References 37 publications

Tetramethylpyrazine reduces inflammation levels and the apoptosis of LPS‑stimulated human periodontal ligament cells via the downregulation of miR‑302b

Tetramethylpyrazine reduces inflammation levels and the apoptosis of LPS‑stimulated human periodontal ligament cells via the downregulation of miR‑302b

The regulatory effect of microRNA-21a-3p on the promotion of telocyte angiogenesis mediated by PI3K (p110α)/AKT/mTOR in LPS induced mice ARDS

LINC00473 exacerbates osteoarthritis development by promoting chondrocyte apoptosis and proinflammatory cytokine production through the miR‑424‑5p/LY6E axis

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