Interleukin‐1α, ‐6, and ‐8 decrease Cdc42 activity resulting in loss of articular chondrocyte phenotype

Novakofski, Kira D.; Torre, Christopher J.; Fortier, Lisa A.

doi:10.1002/jor.21515

Cited by 25 publications

(28 citation statements)

References 38 publications

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“…Exposure to Il6 recapitulates select effects of Notch in chondrocytes, and we tested whether Notch signaling regulates Il6 expression in chondrocyte-enriched cells from Rosa Notch mice infected with Ad-CMV-Cre to induce NICD or with control Ad-CMV-GFP 26,27,28,29 . Analysis of mRNA levels by qRT-PCR revealed that activation of Notch signaling induced a 7 fold increase in Il6 expression (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Exposure of chondrocytes to Il6 phenocopies selected effects of Notch signaling, and we asked whether Il6 mediates the effects of Notch on the expression of chondrocyte gene markers 27,28,29 . To investigate this possibility, chondrocyte-enriched cells from Rosa Notch mice were exposed to a neutralizing murine monoclonal IgG raised against Il6 or murine IgG, either in the context of Notch activation or under basal conditions.…”

Section: Resultsmentioning

confidence: 99%

“…Notch induces Il6 expression in cells of mesenchymal origin, and exposure of bovine, rabbit, and human chondrocytes to Il6 phenocopies selected effects of Notch in murine chondrocytes 26,27,28,29 . In this study, we investigated whether Notch regulates Il6 expression in chondrocytes and whether Il6 mediates the effects of Notch in these cells.…”

Section: Introductionmentioning

confidence: 98%

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Interleukin 6 mediates selected effects of Notch in chondrocytes

Zanotti

Canalis

2013

Osteoarthritis and Cartilage

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Objective Notch receptors determine cell fate by regulating transcription, an event mediated by the Notch intracellular domain (NICD), which is generated by proteolysis brought about by Notch-ligand interactions. Since Notch activation or exposure to interleukin (Il)6 have similar effects in chondrocytes, we explored whether Il6 contributes to the mechanisms of Notch action in these cells. Method NICD was overexpressed in primary chondrocytes from RosaNotch mice, where the Rosa26 promoter precedes a loxP-flanked STOP cassette followed by the NICD coding sequence. Cells were infected with adenoviral vectors expressing Cre to induce NICD or green fluorescent protein as control. Gene expression was determined by quantitative reverse-transcription polymerase chain reaction. Il6 protein concentration in the culture media was determined by enzyme-linked immunosorbent assay. To test the mechanisms of Notch action on Il6 expression, cells were transfected with a fragment of the Il6 promoter or control vector pGL3, or transcriptionally arrested with 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole. Il6 was inhibited with a neutralizing antibody, whereas a normal immunoglobulin G was used as control. Results NICD induced Il6 mRNA and protein, and transactivated the Il6 promoter without affecting Il6 mRNA stability. Il6 neutralization had no impact on gene expression under basal conditions, and did not modify the effects of NICD on sex determining region-Y-related high mobility group-box gene 9, collagen type II α1 and collagen type X α1 expression. Conversely, Il6 neutralization opposed aggrecan (Acan) suppression and prevented matrix metalloprotease (Mmp)13 induction by NICD. Conclusion Il6 mediates suppression of Acan and induction of Mmp13 expression by Notch in chondrocytes.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Interleukin 6 mediates selected effects of Notch in chondrocytes

Zanotti

Canalis

2013

Osteoarthritis and Cartilage

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“…The pathophysiology of osteoarthritis is still unclear, but evidences have proved that pro-inflammatory cytokines produced from cartilage are released into synovial space and participate in the breakdown of articular cartilage, collagen fibers, ligaments and menisci [20,21]. Herein, ATDC5 cells were subjected to LPS to induce an in vitro model of cartilage damage.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Protects Murine Chondrogenic ATDC5 Cells Against LPS-Induced Inflammatory Injury Through Up-Regulating MiR-146b

Jin

Zhang²,

et al. 2018

Cell Physiol Biochem

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Background/Aims: Resveratrol (RSV) has been reported as a promising oral supplementation for osteoarthritis treatment, while the mechanism of its action is still unclear. The specific aim of this study is to decode one of the mechanisms by which RSV protects chondrocyte. Methods: Mouse chondrogenic cell line ATDC5 was treated with 30 µM RSV for 24 h, and 10 µg/ml LPS for 12 h, after which cell viability, apoptosis, and the release of pro-inflammatory cytokines were assessed. The expression of miR-146b in ATDC5 cells was silenced by the specific inhibitor transfection, and then cell viability, apoptosis and inflammation were re-assessed. Results: The IC50 value of LPS in ATDC5 cells was about 10.27 µg/ml. LPS with a dosage of 10 µg/ml repressed cell viability, induced apoptosis, and increased the release of IL-1β, IL-6 and TNF-α. RSV pre-treatment (30 µM) significantly alleviated LPS-induced apoptosis and inflammation. More importantly, miR-146b was up-regulated by RSV, and the protective functions of RSV on ATDC5 cells were attenuated by miR-146b silence. Further, NF-κB and p38MAPK pathways were activated by LPS, and were deactivated by RSV. Besides, RSV-induced the deactivation of NF-κB and p38MAPK pathways was reversed by miR-146b silence. Conclusions: Our findings suggest that RSV protects ATDC5 cells from LPS-induced inflammatory and apoptotic injury via up-regulation of miR-146b and thereby deactivation of NF-κB and p38MAPK pathways.

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“…Integrin signaling has been shown to induce inflammatory cytokines [27,28] www.futuremedicine.com and in various cell types actin cytoskeletal remodeling has been shown to regulate cytokine secretion [29] and potentiate NF-kB signaling [30]. Although this has not been shown for chondrocytes, inflammatory cytokines have been shown to modulate the chondrocyte actin cytoskeleton [31], and, possibly, cytoskeletal remodeling in turn also affects cytokine production and/or secretion in this cell type. For cartilage regeneration using nonexpanded chondrocytes, the HyStem scaffold seemed most optimal.…”

Section: Polyactive™mentioning

confidence: 99%