Down-regulation of microRNA-203a suppresses IL-1β-induced inflammation and cartilage degradation in human chondrocytes through Smad3 signaling

Abstract Osteoarthritis (OA) is a chronic and prevalent degenerative musculoskeletal disorder, which is characterized by articular cartilage degradation and joint inflammation. MicroRNA-203a (miR-203a) has been shown to be involved in multiple pathological processes during OA, but little is known about its function in chondrocyte extracellular matrix (ECM) degradation. In the present study, we aimed to elucidate the effects of miR-203a on articular cartilage degradation and joint inflammation. We observed that the miR-203a level was significantly up-regulated in OA tissues and in an in vitro model of OA, respectively. Inhibition of miR-203a significantly alleviated the interleukin (IL)-1β-induced inflammatory response and ECM degradation in chondrocytes. Moreover, mothers against decapentaplegic homolog 3 (Smad3), a key factor in maintaining chondrocyte homeostasis, was identified as a putative target of miR-203a in chondrocytes. More importantly, inhibition of Smad3 impaired the inhibitory effects of the miR-203a on IL-1β-induced inflammatory response and ECM degradation. Collectively, these results demonstrated that miR-203a may contribute to articular cartilage degradation of OA by targeting Smad3, suggesting a novel therapeutic target for the treatment of OA.

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In Vitro Model of Human Articular Cartilage Degradation

Inflammation Protocols ◽

10.1385/1-59259-374-7:99 ◽

2003 ◽

pp. 99-106 ◽

Cited By ~ 1

Author(s):

William D. Shingleton

Keyword(s):

Articular Cartilage ◽

In Vitro Model ◽

Cartilage Degradation ◽

Human Articular Cartilage ◽

Vitro Model

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Cartilage degradation by macrophages, fibroblasts and synovial cells in culture. An in vitro model suitable for studies on rheumatoid arthritis

Perspectives in Inflammation ◽

10.1007/978-94-011-7185-4_10 ◽

1977 ◽

pp. 115-129 ◽

Cited By ~ 5

Author(s):

G. Vaes ◽

P. Hauser ◽

G. Huybrecht-Godin ◽

C. Peeters-Joris

Keyword(s):

Rheumatoid Arthritis ◽

In Vitro Model ◽

Cartilage Degradation ◽

Synovial Cells ◽

Cells In Culture ◽

Vitro Model

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β-Naphthoflavone and Ethanol Reverse Mitochondrial Dysfunction in A Parkinsonian Model of Neurodegeneration

International Journal of Molecular Sciences ◽

10.3390/ijms21113955 ◽

2020 ◽

Vol 21 (11) ◽

pp. 3955

Author(s):

Jesus Fernandez-Abascal ◽

Elda Chiaino ◽

Maria Frosini ◽

Gavin P. Davey ◽

Massimo Valoti

Keyword(s):

Complex I ◽

In Vitro Model ◽

Inhibitory Effects ◽

Cyp Induction ◽

Cyp Isoforms ◽

Vitro Model ◽

Complex I Activity ◽

Cyp 2D6

The 1-methyl-4-phenylpyridinium (MPP+) is a parkinsonian-inducing toxin that promotes neurodegeneration of dopaminergic cells by directly targeting complex I of mitochondria. Recently, it was reported that some Cytochrome P450 (CYP) isoforms, such as CYP 2D6 or 2E1, may be involved in the development of this neurodegenerative disease. In order to study a possible role for CYP induction in neurorepair, we designed an in vitro model where undifferentiated neuroblastoma SH-SY5Y cells were treated with the CYP inducers β-naphthoflavone (βNF) and ethanol (EtOH) before and during exposure to the parkinsonian neurotoxin, MPP+. The toxic effect of MPP+ in cell viability was rescued with both βNF and EtOH treatments. We also report that this was due to a decrease in reactive oxygen species (ROS) production, restoration of mitochondrial fusion kinetics, and mitochondrial membrane potential. These treatments also protected complex I activity against the inhibitory effects caused by MPP+, suggesting a possible neuroprotective role for CYP inducers. These results bring new insights into the possible role of CYP isoenzymes in xenobiotic clearance and central nervous system homeostasis.

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Beneficial Influence of Platelets on Antibiotic Efficacy in an In Vitro Model of Staphylococcus aureus-Induced Endocarditis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.7.2551-2557.2004 ◽

2004 ◽

Vol 48 (7) ◽

pp. 2551-2557 ◽

Cited By ~ 19

Author(s):

Renee-Claude Mercier ◽

Robert M. Dietz ◽

Jory L. Mazzola ◽

Arnold S. Bayer ◽

Michael R. Yeaman

Keyword(s):

Staphylococcus Aureus ◽

In Vitro Model ◽

Antimicrobial Effect ◽

Human Platelets ◽

Inhibitory Effects ◽

Activated Platelets ◽

Vitro Model ◽

Antibiotic Efficacy ◽

Chamber Fluid

ABSTRACT Platelets contribute to antimicrobial host defense against infective endocarditis (IE) by releasing platelet microbicidal proteins (PMPs). We investigated the influence of thrombin-stimulated human platelets on the evolution of simulated IE in the presence and absence of vancomycin or nafcillin. Staphylococcus aureus strains differing in intrinsic susceptibility to PMPs or antibiotics were studied: ISP479C (thrombin-induced PMP-1 [tPMP-1] susceptible; nafcillin and vancomycin susceptible), ISP479R (tPMP-1 resistant; nafcillin and vancomycin susceptible), and GISA-NJ (tPMP-1 intermediate-susceptible; vancomycin intermediate-susceptible). Platelets were introduced and thrombin activated within the in vitro IE model 30 min prior to inoculation with S. aureus. At 0 to 24 h postinoculation, bacterial densities in chamber fluid and simulated endocardial vegetations (SEVs) were quantified and compared among groups. Activated platelets alone, or in combination with antibiotics, inhibited the proliferation of ISP479C in chamber fluid or SEVs over the initial 4-h period (P < 0.05 versus controls). Moreover, nafcillin-containing regimens exerted inhibitory effects beyond 4 h against ISP479C in both model phases. By comparison, activated platelets inhibited GISA-NJ proliferation in SEVs but not in chamber fluid. The combination of platelets plus nafcillin or vancomycin significantly inhibited proliferation of the GISA-NJ strain in SEVs compared to the effect of platelets or antibiotics alone (P < 0.05). In contrast, platelets did not significantly alter the antistaphylococcal efficacies of nafcillin or vancomycin against ISP479R. These data support our hypothesis that a beneficial antimicrobial effect may result from the interaction among platelets, PMPs, and anti-infective agents against antibiotic-susceptible or -resistant staphylococci that exhibit a tPMP-1-susceptible or -intermediate-susceptible phenotype.

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A three-dimensional in vitro model to quantify inflammatory response to biomaterials

Acta Biomaterialia ◽

10.1016/j.actbio.2014.07.029 ◽

2014 ◽

Vol 10 (11) ◽

pp. 4742-4749 ◽

Cited By ~ 7

Author(s):

Abigail C. Parks ◽

Kevin Sung ◽

Benjamin M. Wu

Keyword(s):

Inflammatory Response ◽

In Vitro Model ◽

Three Dimensional ◽

Vitro Model

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GSK-3 mediates differentiation and activation of proinflammatory dendritic cells

Blood ◽

10.1182/blood-2006-06-028951 ◽

2006 ◽

Vol 109 (4) ◽

pp. 1584-1592 ◽

Cited By ~ 82

Author(s):

Elena Rodionova ◽

Michael Conzelmann ◽

Eugene Maraskovsky ◽

Michael Hess ◽

Michael Kirsch ◽

...

Keyword(s):

Dendritic Cells ◽

In Vitro Model ◽

Glycogen Synthase ◽

Human Monocyte ◽

Glycogen Synthase Kinase 3 ◽

Inhibitory Effects ◽

Tnf Α ◽

Vitro Model

Abstract The key components of the intracellular molecular network required for the expression of a specific function of dendritic cells (DCs) are as yet undefined. Using an in vitro model of human monocyte-derived DC differentiation, this study investigates the role of glycogen synthase kinase 3 (GSK-3), a multifunctional enzyme critical for cellular differentiation, apoptosis, self-renewal, and motility, in this context. We demonstrate that GSK-3 (1) inhibits macrophage development during differentiation of DCs, (2) is constitutively active in immature DCs and suppresses spontaneous maturation, and (3) acquires a proinflammatory functional status mediating high levels of IL-12, IL-6, and TNF-α secretion, and partially inhibits IL-10 in the context of DC activation. In particular, GSK-3 enhances IL-12p35 mRNA expression and thus the production of the proinflammatory cytokine IL-12p70 by integrating the activities of other kinases priming GSK-3 targets and the inhibitory effects of Akt-1. GSK-3 may therefore act as a key integrator of activating and inhibitory pathways involved in proinflammatory DC differentiation and activation.

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MiR-494-3p alleviates acute lung injury through regulating NLRP3 activation by targeting CMPK2

Biochemistry and Cell Biology ◽

10.1139/bcb-2020-0243 ◽

2021 ◽

pp. 1-10

Author(s):

Hong Wang ◽

Shuqin Wang ◽

Shanshan Huang

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Inflammatory Response ◽

Nlrp3 Inflammasome ◽

Cell Apoptosis ◽

In Vitro Model ◽

In Vivo Model ◽

Respiratory Disorder ◽

Vitro Model

Acute lung injury (ALI) is a severe respiratory disorder with a high rate of mortality, and is characterized by excessive cell apoptosis and inflammation. MicroRNAs (miRNAs) play pivotal roles in ALI. This study examined the biological function of miR-494-3p in cell apoptosis and inflammatory response in ALI. For this, mice were injected with lipopolysaccharide (LPS) to generate an in-vivo model of ALI (ALI mice), and WI-38 cells were stimulated with lipopolysaccharide (LPS) to generate an in-vitro model of ALI. We found that miR-494-3p was significantly downregulated in the ALI mice and in the in-vitro model. Overexpression of miR-494-3p inhibited inflammation and cell apoptosis in the LPS-induced WI-38 cells, and improved the symptoms of lung injury in the ALI mice. We then identified cytidine/uridine monophosphate kinase 2 (CMPK2) as a novel target of miR-494-3p in the WI-38 cells. Furthermore, miR-494-3p suppressed cell apoptosis and the inflammatory response in LPS-treated WI-38 cells through targeting CMPK2. The NLRP3 inflammasome is reportedly responsible for the activation of inflammatory processes. In our study, CMPK2 was confirmed to activate the NLRP3 inflammasome in LPS-treated WI-38 cells. In conclusion, miR-494-3p attenuates ALI through inhibiting cell apoptosis and the inflammatory response by targeting CMPK2, which suggests the value of miR-494-3p as a target for the treatment for ALI.

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