miR-152 Attenuates Apoptosis in Chondrocytes and Degeneration of Cartilages in Osteoarthritis Rats via TCF-4 Pathway

Wan, Dafang; Qu, Yang; Ai, Songtao; Cheng, Liming

doi:10.1177/1559325820946918

Cited by 6 publications

(4 citation statements)

References 30 publications

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“…It is widely accepted that IL-1β is involved in the destruction of articular cartilage due to induction of MMPs and ADAMTS, and suppression of IL-1β-induced ECM-degrading enzyme syntheses and secretion results in the chondrocyte ECM breakdown and OA development [53]. Accumulating evidences have demonstrated that multiple miRNAs, such as miR-335-5p, miR-152, and miR-93, are downregulated in OA chondrocytes, and reexpression of miRNAs delay OA progression through enhancing viability, suppressing apoptosis of chondrocytes, and attenuating the inflammatory response with a suppressive effect on TNF-α, IL-1β, and IL-6 [3,13,54]. Another study has also proved that elevated miR-140 elevates collagen II expression and reduces MMP-13 and ADAMTS-5 expressions to inhibit ECM degradation, thereby alleviating OA progression [55].…”

Section: Discussionmentioning

confidence: 99%

“…Mounting evidences indicate that aberrant expression of miRNAs is involved in inflammatory diseases, including OA [11,12]. For instance, miR-152 could protect articular cartilage to suppress OA [13]. Strikingly, miR-3960 is reported to participate in the osteogenic transdifferentiation of vascular smooth muscle cells [14], yet few studies have reported its roles in chondrocyte injury in OA.…”

Section: Introductionmentioning

confidence: 99%

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miR-3960 from Mesenchymal Stem Cell-Derived Extracellular Vesicles Inactivates SDC1/Wnt/β-Catenin Axis to Relieve Chondrocyte Injury in Osteoarthritis by Targeting PHLDA2

Wei

et al. 2022

Stem Cells International

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Osteoarthritis (OA) is a serious disease of the articular cartilage characterized by excessive inflammation. Lately, mesenchymal stem cell- (MSC-) derived extracellular vesicles (EVs) have been proposed as a novel strategy for the treatment of OA. We aimed to investigate the effects of EV-encapsulated miR-3960 derived from MSCs on chondrocyte injury in OA. The cartilage tissues from OA patients were collected to experimentally determine expression patterns of miR-3960, PHLDA2, SDC1, and β-catenin. Next, luciferase assay was implemented to testify the binding affinity among miR-3960 and PHLDA2. EVs were isolated from MSCs and cocultured with IL-1β-induced OA chondrocytes. Afterwards, cellular biological behaviors and levels of extracellular matrix- (ECM-) related protein anabolic markers (collagen II and aggrecan), catabolic markers (MMP13 and ADAMTS5), and inflammatory factors (IL-6 and TNF-α) in chondrocytes were assayed upon miR-3960 and/or PHLDA2 gain- or loss-of-function. Finally, the effects of miR-3960 contained in MSC-derived EVs in OA mouse models were also explored. MSCs-EVs could reduce IL-1β-induced inflammatory response and extracellular matrix (ECM) degradation in chondrocytes. miR-3960 expression was downregulated in cartilage tissues of OA patients but enriched in MSC-derived EVs. miR-3960 could target and inhibit PHLDA2, which was positively correlated with SDC1 and Wnt/β-catenin pathway activation. miR-3960 shuttled by MSC-derived EVs protected against apoptosis and ECM degradation in chondrocytes. In vivo experiment also confirmed that miR-3960 alleviated chondrocyte injury in OA. Collectively, MSC-derived EV-loaded miR-3960 downregulated PHLDA2 to inhibit chondrocyte injury via SDC1/Wnt/β-catenin.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miR-3960 from Mesenchymal Stem Cell-Derived Extracellular Vesicles Inactivates SDC1/Wnt/β-Catenin Axis to Relieve Chondrocyte Injury in Osteoarthritis by Targeting PHLDA2

Wei

et al. 2022

Stem Cells International

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“…Osteoarthritis (OA) is an age-related disease that affects axial and peripheral articulations and weight-bearing joints affecting tens of millions of people all over the world [1]. The disorder is characterized by inflammation of synovial joints, anabolism of articular cartilages, degradation of articular cartilage, improper catabolism, and thickening of subchondral bone [2,3]. In the progression of OA, inflammatory cytokines like IL-1β resulted in tissue injury and articular cartilage degeneration of the OA joints and associated with many pathological processes, including metabolic imbalance, hypertrophy, apoptosis of chondrocytes, and dysregulation of autophagy [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Knockdown of LMX1B Suppressed Cell Apoptosis and Inflammatory Response in IL-1β-Induced Human Osteoarthritis Chondrocytes through NF-κB and NLRP3 Signal Pathway

Wang

et al. 2022

Mediators of Inflammation

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Osteoarthritis (OA), a chronic degenerative joint disease, always occurred in the aging population. There is evidence suggests that chondrocytes’ survival, inflammation, and apoptosis play critical roles in OA pathogenesis. LMX1B has been shown to be involved in antiosteogenic function in early patterning of the calvaria. However, the role and mechanism of LMX1B in OA is not unknown. The present study observed that LMX1B was highly expressed in OA patients compared with normal patients. Besides, we found that IL-1β increased LMX1B mRNA and protein expression in SW1353 and C28/I2 chondrocytes. LMX1B knockdown increased IL-1β-induced cell viability and proliferation and suppressed cell apoptosis and inflammation response, including IFN-γ, TNF-α, IL-6, prostaglandin E2 (PGE2), and NO both in SW1353 and C28/I2. Furthermore, LMX1B silence inhibited MMP-3 and MMP-13 expression both in SW1353 and C28/I2 cells. Also, the activation of the NF-κB and NLRP3 signaling pathway was suppressed in LMX1B silence cells by decreasing the p-p65 and NLRP3 protein expressions. Additionally, inhibition of NF-κB by PDTC suppressed NLRP3 expression. Moreover, NLRP3 overexpression reversed the effects of LMX1B silence on chondrocytes’ survival, proliferation, apoptosis, and inflammation. Finally, we confirmed that LMX1B depletion had protective effects in OA rats in vivo.

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“…CircHIPK3 sponges miR-152-3p to release TGF-β2, thus promoting cardiac fibrosis under hypoxia by regulating fibroblast proliferation and phenotypic switching [ 23 ]. Additionally, miR-152 regulates TCF-4 pathway in OA rats to weaken chondrocyte apoptosis and cartilage degeneration [ 24 ]. StarBase website predicted that miR-152-3p owned putative complementary sites for CASC19.…”

Section: Introductionmentioning

confidence: 99%

LncRNA CASC19 accelerates chondrocytes apoptosis and proinflammatory cytokine production to exacerbate osteoarthritis development through regulating the miR-152-3p/DDX6 axis

Zhou

Chen

2021

J Orthop Surg Res

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Background Osteoarthritis (OA) is one kind of degenerative joint disease that happens in articular cartilage and other joint tissues. Long non-coding RNAs (lncRNAs) have been reported to serve as pivotal regulators in many diseases, including OA. However, the role and relevant regulatory mechanisms of CASC19 in OA remain unknown. Methods The expression levels of CASC19, miR-152-3p, and DDX6 were identified by reverse-transcription polymerase chain reaction (RT-qPCR). Cell viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) and flow cytometry assays, respectively. The relationship between miR-152-3p and CASC19 or DDX6 was predicted by bioinformatics tools and verified by the dual-luciferase reporter assay. Results CASC19 was verified to exhibit higher expression in OA tissues and cells. Moreover, inhibition of CASC19 weakened proinflammatory cytokine (IL-6, IL-8, and TNF-α) production and cell apoptosis but facilitated cell viability. Experiments of the ceRNA mechanism elucidated that miR-152-3p was a sponge for CASC19, and miR-152-3p targeted DDX6, suggesting that CASC19 sponged miR-152-3p to release DDX6. Finally, results from rescue assays proved that the impacts of CASC19 silencing on chondrocytes apoptosis and proinflammatory cytokine production could be reversed by DDX6 overexpression. Conclusions It was concluded that lncRNA CASC19 accelerated chondrocytes apoptosis and proinflammatory cytokine production to exacerbate osteoarthritis development through regulating the miR-152-3p/DDX6 axis. These findings may offer an effective biological target for OA treatment.

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miR-152 Attenuates Apoptosis in Chondrocytes and Degeneration of Cartilages in Osteoarthritis Rats via TCF-4 Pathway

Cited by 6 publications

References 30 publications

miR-3960 from Mesenchymal Stem Cell-Derived Extracellular Vesicles Inactivates SDC1/Wnt/β-Catenin Axis to Relieve Chondrocyte Injury in Osteoarthritis by Targeting PHLDA2

miR-3960 from Mesenchymal Stem Cell-Derived Extracellular Vesicles Inactivates SDC1/Wnt/β-Catenin Axis to Relieve Chondrocyte Injury in Osteoarthritis by Targeting PHLDA2

Knockdown of LMX1B Suppressed Cell Apoptosis and Inflammatory Response in IL-1β-Induced Human Osteoarthritis Chondrocytes through NF-κB and NLRP3 Signal Pathway

LncRNA CASC19 accelerates chondrocytes apoptosis and proinflammatory cytokine production to exacerbate osteoarthritis development through regulating the miR-152-3p/DDX6 axis

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