miR-93-5p attenuates IL-1β-induced chondrocyte apoptosis and cartilage degradation in osteoarthritis partially by targeting TCF4

Xue, Hao; Tu, Yihui; Ma, Tiancai; Wen, Tao; Yang, Tao; Xue, Long; Cai, Minwei; Wang, Fangxing; Guan, Mengying

doi:10.1016/j.bone.2019.03.035

Cited by 49 publications

(30 citation statements)

References 34 publications

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“…Wu et al [27] have pointed out that TCF4 is significantly positively correlated with the joint injury degree of OA patients, suggesting that TCF4 may be involved in the pathological process of OA. The reports by Xue et al [28] have suggested that TCF4 is targeted at miR-93-5p, which mediates the activity and apoptosis of chondrocytes, and inhibition of its expression is helpful to alleviate OA progress. All the above studies have inspired us that miR-137 and TCF4 are probably involved in the regulation of OA disease process and play a key role in it.…”

Section: Discussionmentioning

confidence: 99%

miR-137 targets the inhibition of TCF4 to reverse the progression of osteoarthritis through the AMPK/NF-κB signaling pathway

Wang¹,

Fang²,

Ye³

et al. 2020

Bioscience Reports

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Purpose: To explore the regulatory mechanism of miR-137 and transcription factor 4 (TCF4) in the progression of osteoarthritis (OA). Patients and Methods: The expressions of miR-137 and TCF4 were detected in OA cartilage tissue, chondrocytes and OA rat cartilage tissue. miR-137 and TCF4 were up-regulated or down-regulated and transfected into chondrocytes and OA rat cartilage tissue. The gene expression, protein level, cell proliferation, apoptosis and inflammatory factors were detected, respectively. LPS and anterior cruciate ligament transection (ACLT) on the right knee were used to induce chondrocyte inflammation and establish rat OA model, respectively. Results: miR-137 was low expressed in cartilage tissue of OA group, while TCF4 expression and protein level were significantly higher, showing significant negative correlation. In LPS group, chondrocyte activity was significantly inhibited, cell apoptosis ability was significantly enhanced, and the levels of inflammatory factors TNF-α, IL-1β, IL-6 were significantly increased. However, the above results were significantly improved after the up-regulation of miR-137 or down-regulation of TCF4. Double luciferase report revealed that miR-137 and TCF4 had targeted relationship. LPS induced activation of AMPK/NF-κB pathway and higher level of apoptosis. AMPK/NF-κB pathway inhibitor C could inhibit activation of this pathway, and up-regulation of miR-137 or down-regulation of TCF4 could significantly weaken the regulation of LPS on the pathway and apoptosis. Analysis of OA rat model showed that over-expression of miR-137 could inhibit up-regulation of inflammatory factors and activation of AMPK/NF-κB pathway. Conclusion: miR-137 targets the inhibition of TCF4 to reverse the progression of OA through the AMPK/NF-κB signaling pathway.

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Section: Discussionmentioning

confidence: 99%

miR-137 targets the inhibition of TCF4 to reverse the progression of osteoarthritis through the AMPK/NF-κB signaling pathway

Wang¹,

Fang²,

Ye³

et al. 2020

Bioscience Reports

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“…Other key findings in the miRNA field include the observation that miR-138-mediated inhibition of osteogenesis could be rescued by overexpression of its target RhoC 68 , miR-93e5p may target TCF4 to prevent cartilage matrix degradation 69 , and finally, that miR-324e5p is upregulated in OA and targets the hedgehog signalling pathway in chondrocytes 70 .…”

Section: Micrornasmentioning

confidence: 99%

Osteoarthritis year in review 2019: genetics, genomics and epigenetics

Reynard

Barter

2020

Osteoarthritis and Cartilage

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s u m m a r yAlthough osteoarthritis (OA) aetiology is complex, genetic, genomic and epigenetic studies published within the last decade have advanced our understanding of the molecular processes underlying this common musculoskeletal disease. The purpose of this narrative review is to highlight the key research articles within the OA genetics, genomics and epigenetics fields that were published between April 2018 and April 2019. The review focuses on the identification of new OA genetic risk loci, genomics techniques that have been used for the first time in human cartilage and new publicly available databases, and datasets that will aid OA functional studies.Fifty-six new OA susceptibility loci were identified by two large scale genome wide association study meta-analyses, increasing the number of genome-wide significant risk loci to 90. OA risk variants are enriched near genes involved in skeletal development and morphology, and show genetic overlap with height, hip shape, bone area and developmental dysplasia of the hip. Several functional studies of OA loci were published, including a genome-wide analysis of genetic variation on cartilage gene expression. A specialised data portal for exploring cross-species skeletal transcriptomic datasets has been developed, and the first use of cartilage single cell RNAseq analysis reported. This year also saw the systematic identification of all microRNAs, long non-coding RNAs and circular RNAs expressed in human OA cartilage. Putative transcriptional regulatory regions have been mapped in human chondrocytes genome-wide, providing a dataset that will facilitate the prioritisation and characterisation of OA genetic and epigenetic loci.

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“…in addition, mir-93-5p was revealed to reverse the inflammatory and antiproliferative processes of neodymium oxide-induced human bronchial epithelial cell lines caused by circular rna 0039411 (19). Xue et al (20) noted that mir-93-5p was decreased in il-β-induced chondrocytes and human and rat osteoarthritis-affected cartilage and that introduction of mir-93-5p suppressed cell apoptosis, increased cell viability and maintained cell metabolism balance in il-β-induced chondrocytes. in the present study, mir-93-5p Figure 6.…”

Section: Discussionmentioning

confidence: 98%

“…mir-93-5p has also been implicated in the inflammatory and antiproliferative processes of human bronchial epithelial cell lines induced by neodymium oxide (19). Furthermore, mir-93-5p has been revealed to regulate il-1β-induced cartilage degradation and chondrocyte apoptosis in osteoarthritis (20). However, the role of mir-93-5p in osteoarthritis remains to be elucidated.…”

Section: Knockdown Of Exosome-mediated Lnc-pvt1 Alleviates Lipopolysamentioning

confidence: 99%

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

et al. 2020

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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.

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miR-93-5p attenuates IL-1β-induced chondrocyte apoptosis and cartilage degradation in osteoarthritis partially by targeting TCF4

Cited by 49 publications

References 34 publications

miR-137 targets the inhibition of TCF4 to reverse the progression of osteoarthritis through the AMPK/NF-κB signaling pathway

miR-137 targets the inhibition of TCF4 to reverse the progression of osteoarthritis through the AMPK/NF-κB signaling pathway

Osteoarthritis year in review 2019: genetics, genomics and epigenetics

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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