Resistin induces expression of pro-inflammatory cytokines and chemokines in human articular chondrocytes via transcription and mRNA stabilization

Objective In osteoarthritis, chondrocytes tend to acquire a hypertrophic phenotype, which contributes to the modification of the extracellular matrix, resulting in permanent cartilage changes. In mouse chondrocytes, pro-inflammatory macrophages and pro-inflammatory cytokines have been shown to stimulate hypertrophy via the activation of the nuclear factor kappa B (NF-κB) pathway. Whether or not this also occurs in human chondrocytes remains unclear. We therefore aimed to investigate whether hypertrophy-like responses in human cartilage are driven mainly by intrinsic inflammatory signaling or shaped by specific macrophage populations. Design Human articular chondrocytes were cultured with pro-inflammatory cytokines or medium conditioned by defined macrophage subsets. Furthermore, the effect of inhibition of NF-κB-dependent gene expression was evaluated using the NF-κB inhibitor SC-514. Hypertrophy was assessed by measuring the transcription level of alkaline phosphatase ( ALPL), type X collagen ( COL10A1), Indian hedgehog ( IHH), and runt-related transcription factor 2 ( RUNX2). Results The expression of hypertrophic genes was not promoted in human chondrocytes by pro-inflammatory cytokines neither pro-inflammatory M(IFNγ + TNFα) macrophages. Inhibition of the NF-κB-dependent gene expression did not affect human articular chondrocyte hypertrophy. However, tissue repair M(IL4) macrophages induced hypertrophy by promoting the expression of COL10A1, RUNX2, and IHH. Conclusion Intrinsic inflammatory signaling activation is not involved in the hypertrophic shift observed in human articular chondrocytes cultured in vitro. However, tissue repair macrophages may contribute to the onset of this detrimental phenotype in human osteoarthritic cartilage, given the effect observed in our experimental models.

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Concentration-Dependent Effects of Cobalt and Chromium Ions on Osteoarthritic Chondrocytes

Cartilage ◽

10.1177/1947603519889389 ◽

2019 ◽

pp. 194760351988938

Author(s):

Christoph Bauer ◽

Christoph Stotter ◽

Vivek Jeyakumar ◽

Eugenia Niculescu-Morzsa ◽

Bojana Simlinger ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Metabolic Activity ◽

Transcriptional Activity ◽

Articular Chondrocytes ◽

Inflammatory Responses ◽

Quantitative Polymerase Chain Reaction ◽

Human Articular Chondrocytes ◽

Tnf Α ◽

Late Apoptosis ◽

Pro Inflammatory Cytokines

Objective Cobalt and chromium (CoCr) ions from metal implants are released into the joint due to biotribocorrosion, inducing apoptosis and altering gene expression in various cell types. Here, we asked whether CoCr ions concentration-dependently changed viability, transcriptional activity, and inflammatory response in human articular chondrocytes. Design Human articular chondrocytes were exposed to Co (1.02-16.33 ppm) and Cr (0.42-6.66 ppm) ions and cell viability and early/late apoptosis (annexin V and 7-AAD) were assessed in 2-dimensional cell cultures using the XTT assay and flow cytometry, respectively. Changes in chondrocyte morphology were assessed using transmitted light microscopy. The effects of CoCr ions on transcriptional activity of chondrocytes were evaluated by quantitative polymerase chain reaction (qPCR). The inflammatory responses were determined by measuring the levels of released pro-inflammatory cytokines (interleukin-1β [IL-1β], IL-6, IL-8, and tumor necrosis factor–α [TNF-α]). Results CoCr ions concentration-dependently reduced metabolic activity and induced early and late apoptosis after 24 hours in culture. After 72 hours, the majority of chondrocytes (>90%) were apoptotic at the highest concentrations of CoCr ions (16.33/6/66 ppm). SOX9 expression was concentration-dependently enhanced, whereas expression of COL2A1 linearly decreased after 24 hours. IL-8 release was enhanced proportionally to CoCr ions levels, whereas IL-1β, IL-6, and TNF-α levels were not affected by the treatments. Conclusions CoCr ions showed concentration- and time-dependent effects on articular chondrocytes. Fractions of apoptotic articular chondrocytes were proportional to CoCr ion concentrations. In addition, metabolic activity and expression of chondrocyte-specific genes were decreased by CoCr ions. Furthermore, exposure to CoCr ions caused a release of pro-inflammatory cytokines.

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Influence of bisphosphonates on the production of pro-inflammatory cytokines by activated human articular chondrocytes

Cytokine ◽

10.1016/j.cyto.2005.05.009 ◽

2005 ◽

Vol 31 (4) ◽

pp. 298-304 ◽

Cited By ~ 15

Author(s):

Jan F. Van Offel ◽

Evelyne J. Dombrecht ◽

Chris H. Bridts ◽

Annemie J. Schuerwegh ◽

Didier G. Ebo ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Articular Chondrocytes ◽

Human Articular Chondrocytes ◽

Pro Inflammatory Cytokines

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Regulation of SOX9 mRNA in Human Articular Chondrocytes Involving p38 MAPK Activation and mRNA Stabilization

Journal of Biological Chemistry ◽

10.1074/jbc.m604322200 ◽

2006 ◽

Vol 281 (51) ◽

pp. 39471-39479 ◽

Cited By ~ 76

Author(s):

Simon R. Tew ◽

Timothy E. Hardingham

Keyword(s):

P38 Mapk ◽

Articular Chondrocytes ◽

Human Articular Chondrocytes ◽

Mapk Activation ◽

Mrna Stabilization

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Associations between HBD3 and Pro-Inflammatory Cytokines in Asymptomatic Irreversible Pulpitis

Edelweiss Applied Science and Technology ◽

10.33805/2572-6978.105 ◽

2017 ◽

pp. 14-19

Author(s):

Anita Aminoshariae ◽

Mohammed Bakkar ◽

Tracey Bonfield ◽

Santosh Ghosh ◽

Thomas A Montagnese ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Normal Group ◽

Control Group ◽

Spearman Correlation ◽

Whitney Test ◽

Cytokines And Chemokines ◽

Luminex Technology ◽

Spearman Correlation Test ◽

Irreversible Pulpitis ◽

Pro Inflammatory Cytokines

Objective: The aim of this study was to investigate the levels of Human Beta Defensin (hBD) 2 and 3, chemokine and cytokine expressions between teeth endodontically diagnosed with symptomatic irreversible pulpitis (SIP), asymptomatic irreversible pulpitis (ASIP) and normal pulps. We hypothesized that there would be a correlation between hBD’s and the immunoregulatory response. Design: Pulpal samples were collected with paper points. Six samples were obtained from normal teeth, 21 from SIP, 18 from ASIP. Levels of cytokines and betadefensins were measured by Luminex technology and ELISA, respectively. Data were statistically analyzed using Kruskal-Wallis, Wilcoxon Mann-Whitney test and Spearman correlation test. Differences were considered significant at p<0.05. Results: hBD-2 levels correlated with samples obtained from patients in the ASIP group, but not in the samples obtained from patients with SIP or the control group. HBD-3 concentrations associated with all of the cytokines and chemokines in both SIP and ASIP groups. However, in the normal group, hBD-3 correlated with only TNFα, IL-8, MCP-1, IL-1β, MIP-1a, RANTES, IL-17 in normal group. When comparing control levels of hBD-2 and hBD-3 with patients samples from either the ASIP or the SIP groups, hBD-2 and hBD-3 concentrations were highest in the ASIP group. Conclusions: The hBD-2 and-3 were highly associated with the levels of the chemokines and cytokines in ASIP group. HBD-3 concentrations correlate with the levels of the chemokines and the cytokines in the SIP and ASIP groups.

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Response of young, aged and osteoarthritic human articular chondrocytes to inflammatory cytokines: molecular and cellular aspects

Matrix Biology ◽

10.1016/s0945-053x(02)00028-8 ◽

2002 ◽

Vol 21 (5) ◽

pp. 449-459 ◽

Cited By ~ 84

Author(s):

Beatrice Dozin ◽

Mara Malpeli ◽

Laura Camardella ◽

Ranieri Cancedda ◽

Antonello Pietrangelo

Keyword(s):

Inflammatory Cytokines ◽

Articular Chondrocytes ◽

Human Articular Chondrocytes

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GSK5182, 4-Hydroxytamoxifen Analog, a New Potential Therapeutic Drug for Osteoarthritis

Pharmaceuticals ◽

10.3390/ph13120429 ◽

2020 ◽

Vol 13 (12) ◽

pp. 429

Author(s):

Yunhui Min ◽

Dahye Kim ◽

Godagama Gamaarachchige Dinesh Suminda ◽

Xiangyu Zhao ◽

Mangeun Kim ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Small Molecule ◽

Articular Chondrocytes ◽

Therapeutic Potential ◽

Inverse Agonist ◽

Therapeutic Drug ◽

Articular Chondrocyte ◽

Orphan Nuclear Receptors ◽

Genetic Ablation ◽

Pro Inflammatory Cytokines

Estrogen-related receptors (ERRs) are the first identified orphan nuclear receptors. The ERR family consists of ERRα, ERRβ, and ERRγ, regulating diverse isoform-specific functions. We have reported the importance of ERRγ in osteoarthritis (OA) pathogenesis. However, therapeutic approaches with ERRγ against OA associated with inflammatory mechanisms remain limited. Herein, we examined the therapeutic potential of a small-molecule ERRγ inverse agonist, GSK5182 (4-hydroxytamoxifen analog), in OA, to assess the relationship between ERRγ expression and pro-inflammatory cytokines in mouse articular chondrocyte cultures. ERRγ expression increased following chondrocyte exposure to various pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Pro-inflammatory cytokines dose-dependently increased ERRγ protein levels. In mouse articular chondrocytes, adenovirus-mediated ERRγ overexpression upregulated matrix metalloproteinase (MMP)-3 and MMP-13, which participate in cartilage destruction during OA. Adenovirus-mediated ERRγ overexpression in mouse knee joints or ERRγ transgenic mice resulted in OA. In mouse joint tissues, genetic ablation of Esrrg obscured experimental OA. These results indicate that ERRγ is involved in OA pathogenesis. In mouse articular chondrocytes, GSK5182 inhibited pro-inflammatory cytokine-induced catabolic factors. Consistent with the in vitro results, GSK5182 significantly reduced cartilage degeneration in ERRγ-overexpressing mice administered intra-articular Ad-Esrrg. Overall, the ERRγ inverse agonist GSK5182 represents a promising therapeutic small molecule for OA.

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