ArticlePloS one2015
Differentially Expressed in Chondrocytes 2 (DEC2) Increases the Expression of IL-1β and Is Abundantly Present in Synovial Membrane in Rheumatoid Arthritis.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- TNFα-Related Chondrocyte Inflammation Models: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Long Non-Coding RNAsCurrent issues in molecular biology · 2026Article
- BHLHE41, a transcriptional repressor involved in physiological processes and tumor development.Cellular oncology (Dordrecht, Netherlands) · 2025Review
- Role of differentiated embryo-chondrocyte expressed gene 2 in immunity.Frontiers in immunology · 2024Review
- Obstructive sleep apnea-increased DEC1 regulates systemic inflammation and oxidative stress that promotes development of pulmonary arterial hypertension.Apoptosis : an international journal on programmed cell death · 2023Article
- IL-17A and TNF synergistically drive expression of proinflammatory mediators in synovial fibroblasts via IκBζ-dependent induction of ELF3.Rheumatology (Oxford, England) · 2023Article
- Mesangial Cells in Lupus Nephritis.Current rheumatology reports · 2022Review
- Article
- The Potential Roles of Dec1 and Dec2 in Periodontal Inflammation.International journal of molecular sciences · 2021Review
- A Bioinformatics Model of Human Diseases on the Basis of Differentially Expressed Genes (of Domestic Versus Wild Animals) That Are Orthologs of Human Genes Associated with Reproductive-Potential Changes.International journal of molecular sciences · 2021Article
- Disruptive Selection of Human Immunostimulatory and Immunosuppressive Genes Both Provokes and Prevents Rheumatoid Arthritis, Respectively, as a Self-Domestication Syndrome.Frontiers in genetics · 2021Article
- Long non-coding NR2F1-AS1 is associated with tumor recurrence in estrogen receptor-positive breast cancers.Molecular oncology · 2020Article
- Downregulation of DEC1 by RNA interference attenuates ischemia/reperfusion-induced myocardial inflammation by inhibiting the TLR4/NF-κB signaling pathway.Experimental and therapeutic medicine · 2020Article
- Moxibustion benignantly regulates circadian rhythm of REV-ERBα in RA rats.American journal of translational research · 2020Review
- Overexpression of BHLHE41, correlated with DNA hypomethylation in 3'UTR region, promotes the growth of human clear cell renal cell carcinoma.Oncology reports · 2019Article
- Experimental study of TNF-α receptor gene transfection by ultrasound-targeted microbubble destruction to treat collagen-induced arthritis in ratsExperimental and therapeutic medicine · 2019Article
- Contribution of the clock gene DEC2 to VEGF mRNA upregulation by modulation of HIF1α protein levels in hypoxic MIO-M1 cells, a human cell line of retinal glial (Müller) cells.Japanese journal of ophthalmology · 2018Article
- Melatonin in regulation of inflammatory pathways in rheumatoid arthritis and osteoarthritis: involvement of circadian clock genes.British journal of pharmacology · 2018Review
- Regulation of B-1a cells: another novel function of the basic helix-loop-helix transcriptional regulator BHLHE41.Cellular & molecular immunology · 2017Article
- DEC2 Blocks the Effect of the ARNTL2/NPAS2 Dimer on the Expression of PER3 and DBP.Journal of circadian rhythms · 2017Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivePatients with rheumatoid arthritis (RA) have altered circadian rhythm of circulating serum cortisol, melatonin and IL-6, as well as disturbance in the expression of clock genes ARNTL2 and NPAS2. In humans, TNFα increases the expression ARNTL2 and NPAS2 but paradoxically suppresses clock output genes DPB and PER3. Our objective was to investigate the expression of direct clock suppressors DEC1 and DEC2 (BHLHE 40 and 41 proteins) in response to TNFα and investigate their role during inflammation.
methodsCultured primary fibroblasts were stimulated with TNFα. Effects on DEC2 were studied using RT-qPCR and immunofluorescence staining. The role of NF-κB in DEC2 increase was analyzed using IKK-2 specific inhibitor IMD-0354. Cloned DEC2 was transfected into HEK293 cells to study its effects on gene expression. Transfections into primary human fibroblasts were used to confirm the results. The presence of DEC2 was analyzed in (RA) and osteoarthritis (OA) synovial membranes by immunohistochemistry.
resultsTNFα increased DEC2 mRNA and DEC2 was mainly detected at nuclei after the stimulus. The effects of TNFα on DEC2 expression were mediated via NF-κB. Overexpression, siRNA and promoter activity studies disclosed that DEC2 directly regulates IL-1β, in both HEK293 cells and primary human fibroblasts. DEC2 was increased in synovial membrane in RA compared to OA.
conclusionNot only ARNTL2 and NPAS2 but also DEC2 is regulated by TNFα in human fibroblasts. NF-κB mediates the effect on DEC2, which upregulates IL-1β. Circadian clock has a direct effect on inflammation in human fibroblasts.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.