Fibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritis.
Open Biol
; 14(7): 240089, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38981514
ABSTRACT
Rheumatoid arthritis is a chronic inflammatory disease that shows characteristic diurnal variation in symptom severity, where joint resident fibroblast-like synoviocytes (FLS) act as important mediators of arthritis pathology. We investigate the role of FLS circadian clock function in directing rhythmic joint inflammation in a murine model of inflammatory arthritis. We demonstrate FLS time-of-day-dependent gene expression is attenuated in arthritic joints, except for a subset of disease-modifying genes. The deletion of essential clock gene Bmal1 in FLS reduced susceptibility to collagen-induced arthritis but did not impact symptomatic severity in affected mice. Notably, FLS Bmal1 deletion resulted in loss of diurnal expression of disease-modulating genes across the joint, and elevated production of MMP3, a prognostic marker of joint damage in inflammatory arthritis. This work identifies the FLS circadian clock as an influential driver of daily oscillations in joint inflammation, and a potential regulator of destructive pathology in chronic inflammatory arthritis.
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Base de dados:
MEDLINE
Assunto principal:
Artrite Experimental
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Ritmo Circadiano
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Fatores de Transcrição ARNTL
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Fibroblastos
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Sinoviócitos
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article