ArticleArthritis research & therapy2012
Disruption of rhythms of molecular clocks in primary synovial fibroblasts of patients with osteoarthritis and rheumatoid arthritis, role of IL-1β/TNF.
Article in Arthritis research & therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 71 citations in OpenAlex.
- Fibroblast-like Synoviocytes as Key Regulators of Homeostasis and Inflammation in the Joint Microenvironment of Inflammatory Arthritis.Biomedicines · 2026Article
- Bmal1 Attenuates Collagen-Induced Arthritis by Regulating Macrophage Polarization via Sirt1.Journal of inflammation research · 2026Article
- The brain-gut-joint axis in arthritis: crosstalk, treatment, and future perspectives.Journal of orthopaedic translation · 2026Review
- Dual-responsive synthetic gene circuit for dynamic biologic drug delivery via inflammatory and circadian signaling pathways.Journal of biological engineering · 2025Review
- The circadian rhythm as therapeutic target in inflammatory bowel disease.Journal of the Canadian Association of Gastroenterology · 2025Article
- The role of circadian rhythm regulator PERs in oxidative stress, immunity, and cancer development.Cell communication and signaling : CCS · 2025Review
- Article
- Inflammation o'clock: interactions of circadian rhythms with inflammation-induced skeletal muscle atrophy.The Journal of physiology · 2024Review
- Similarities and differences between osteoarthritis and rheumatoid arthritis: insights from Mendelian randomization and transcriptome analysis.Journal of translational medicine · 2024Article
- Exacerbating effects of circadian rhythm disruption on the systemic lupus erythematosus.Lupus science & medicine · 2024Article
- Chronic Inflammation Disrupts Circadian Rhythms in Splenic CD4+ and CD8+ T Cells in Mice.Cells · 2024Article
- The Role of Clock Genes in Maintaining Circadian Rhythm and Rheumatoid Arthritis Pathophysiology.Cureus · 2023Review
- Icariin alleviates osteoarthritis through PI3K/Akt/mTOR/ULK1 signaling pathway.European journal of medical research · 2022Article
- Rhythm disturbance in osteoarthritis.Cell communication and signaling : CCS · 2022Review
- Adaptive immunity, chronic inflammation and the clock.Seminars in immunopathology · 2022Review
- The therapeutic effect and mechanism of melatonin on osteoarthritis: From the perspective of non-coding RNAs.Frontiers in genetics · 2022Review
- Identifying hub circadian rhythm biomarkers and immune cell infiltration in rheumatoid arthritis.Frontiers in immunology · 2022Article
- Screening of anti-chronic nonbacterial prostatitis activity of different extractions of the aerial part ofBiomedical reports · 2021Article
- Morphofunctional State and Circadian Rhythms of the Liver under the Influence of Chronic Alcohol Intoxication and Constant Lighting.International journal of molecular sciences · 2021Article
- Chronobiology and Chronotherapy in Inflammatory Joint Diseases.Pharmaceutics · 2021Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionCircadian rhythms play an important role in the body and in single cells. Rhythms of molecular clocks have not been investigated in synovial fibroblasts (SF) of patients with osteoarthritis (OA) and rheumatoid arthritis (RA). The study was initiated to fill this gap and to study effects of interleukin (IL)-1β/tumor necrosis factor (TNF) on rhythmicity in synovial fibroblasts of RA and OA patients.
methodsThe presence of BMAL-1, CLOCK, Period 1 and Period 2 proteins in synovial tissue was investigated by immunofluorescence. The presence of mRNA of molecular clocks was studied during 72 h by qPCR. Characteristics of rhythms were studied with time series analysis.
resultsBMAL-1, CLOCK, Period 1 and Period 2 proteins were abundantly present in synovial tissue of OA, RA and controls. Receiving synovial tissue at different operation time points during the day (8:00 am to 4:00 pm) did not reveal a rhythm of BMAL-1 or Period 1 protein. In OASF and RASF, no typical rhythm curve of molecular clock mRNA was observed. Time series analysis identified a first peak between 2 and 18 hours after synchronization but a period was not detectable due to loss of rhythm. TNF inhibited mRNA of CLOCK, Period 1 and Period 2 in OASF, while IL-1β and TNF increased these factors in RASF. This was supported by dose-dependently increased levels in MH7A RA fibroblasts. In RASF, IL-1β and TNF shifted the first peak of BMAL-1 mRNA to later time points (8 h to 14 h).
conclusionRhythmicity is not present in primary OASF and RASF, which is unexpected because fibroblasts usually demonstrate perfect rhythms during several days. This might lead to uncoupling of important cellular pathways.
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