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bioRxiv · 10.1101/2024.04.02.587439

Fibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritis

Downton, P.·Dickson, S. H.·Ray, D. W.·Bechtold, D. A.·Gibbs, J. E.
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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. Deletion of essential clock gene Bmal1 in FLS reduced susceptibility to collagen-induced arthritis (CIA), 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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Downton, P., Dickson, S. H., Ray, D. W., Bechtold, D. A., Gibbs, J. E.. 2024-04-03. Fibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritis. https://doi.org/10.1101/2024.04.02.587439

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