| Title: |
Fibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritis |
| Authors: |
Downton, P; Dickson, SH; Ray, DW; Bechtold, DA; Gibbs, JE |
| Publisher Information: |
The Royal Society |
| Publication Year: |
2024 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.1098/rsob.240089 |
| DOI: |
10.1098/rsob.240089 |
| Availability: |
https://doi.org/10.1098/rsob.240089; https://ora.ox.ac.uk/objects/uuid:396502ed-2918-4da3-a05c-ca1cb77cc5fb |
| Rights: |
info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| Accession Number: |
edsbas.4799D8AB |
| Database: |
BASE |