ArticleArthritis research & therapy2019
The circadian regulator Bmal1 in joint mesenchymal cells regulates both joint development and inflammatory arthritis.
Article in Arthritis research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 47 citations in OpenAlex.
- Article
- A temporal dialogue between the circadian clock and chronic inflammatory diseases.Disease models & mechanisms · 2026Review
- Bmal1 Attenuates Collagen-Induced Arthritis by Regulating Macrophage Polarization via Sirt1.Journal of inflammation research · 2026Article
- Dual roles of circadian clock proteins in development and adult homeostasis.Npj biological timing and sleep · 2026Review
- Pharmacist-Driven Chondroprotection in Osteoarthritis: A Multifaceted Approach Using Patient Education, Information Visualization, and Lifestyle Integration.Pharmacy (Basel, Switzerland) · 2025Review
- Article
- Signaling pathway mechanisms of circadian clock gene Bmal1 regulating bone and cartilage metabolism: a review.Bone research · 2025Review
- Unveiling the novel role of circadian rhythms in sepsis and septic shock: unexplored implications for chronotherapy.Frontiers in endocrinology · 2025Review
- Natural Compounds for Preventing Age-Related Diseases and Cancers.International journal of molecular sciences · 2024Review
- Fibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritis.Open biology · 2024Article
- Circadian clock-related genome-wide mendelian randomization identifies putatively genes for ulcerative colitis and its comorbidity.BMC genomics · 2024Article
- Melatonin and bone-related diseases: an updated mechanistic overview of current evidence and future prospects.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2023Review
- Circadian disruption in lung fibroblasts enhances NF-κB activity to exacerbate neutrophil recruitment.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Effect of Circadian Rhythm Disturbance on the Human Musculoskeletal System and the Importance of Nutritional Strategies.Nutrients · 2023Review
- Circadian rhythms in psoriasis and the potential of chronotherapy in psoriasis management.Experimental dermatology · 2022Review
- Rhythm disturbance in osteoarthritis.Cell communication and signaling : CCS · 2022Review
- BMAL1 moonlighting as a gatekeeper for LINE1 repression and cellular senescence in primates.Nucleic acids research · 2022Article
- Adaptive immunity, chronic inflammation and the clock.Seminars in immunopathology · 2022Review
- Circadian rhythms in adaptive immunity and vaccination.Seminars in immunopathology · 2022Review
- Chrono-moxibustion adjusts circadian rhythm of CLOCK and BMAL1 in adjuvant-induced arthritic rats.American journal of translational research · 2022Article
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5 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe circadian clock plays a crucial role in regulating physiology and is important for maintaining immune homeostasis and responses to inflammatory stimuli. Inflammatory arthritis often shows diurnal variation in disease symptoms and disease markers, and it is now established that cellular clocks regulate joint inflammation. The clock gene Bmal1 is critical for maintenance of 24-h rhythms and plays a key role in regulating immune responses, as well as in aging-related processes. Fibroblast-like synoviocytes (FLS) are circadian rhythmic joint mesenchymal cells which are important for maintenance of joint health and play a crucial role in the development of inflammatory arthritis. The aim of this study was to investigate the importance of the joint mesenchymal cell circadian clock in health and disease.
methodsMice were generated which lack Bmal1 in Col6a1-expressing cells, targeting mesenchymal cells in the ankle joints. Joints of these animals were assessed by X-ray imaging, whole-mount staining and histology, and the composition of the synovium was assessed by flow cytometry. Arthritis was induced using collagen antibodies.
resultsBmal1 deletion in joint mesenchymal cells rendered the FLS and articular cartilage cells arrhythmic. Targeted mice exhibited significant changes in the architecture of the joints, including chondroid metaplasia (suggesting a switch of connective tissue stem cells towards a chondroid phenotype), reductions in resident synovial macrophages and changes in the basal pro-inflammatory activity of FLS. Loss of Bmal1 in FLS rendered these resident immune cells more pro-inflammatory in response to challenge, leading to increased paw swelling, localised infiltration of mononuclear cells and enhanced cytokine production in a model of arthritis.
conclusionsThis study demonstrates the importance of Bmal1 in joint mesenchymal cells in regulating FLS and chondrocyte development. Additionally, we have identified a role for this core clock component for restraining local responses to inflammation and highlight a role for the circadian clock in regulating inflammatory arthritis.
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