Featured Publication in Focus: Fibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritis

Authors:

Polly Downton, Suzanna H. Dickson, David W. Ray, David A. Bechtold and Julie E. Gibbs

 

Centre for Biological Timing, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK

 

Open Biology. The Royal Society Publishing

 

----------------------

Products referenced:

Catalogue # 804001-sol

Collagen Type II, Bovine, Immunization Grade, Soluble, 2 mg/mL

Catalogue # 501009

Complete Freund's Adjuvant, 4 mg/mL (5 mL)

----------------------

 

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.

 

To continue reading and to download the publication:

https://doi.org/10.1098/rsob.240089