Fibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritis
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 rhyt...
| मुख्य लेखकों: | , , , , |
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| स्वरूप: | Journal article |
| भाषा: | English |
| प्रकाशित: |
The Royal Society
2024
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| _version_ | 1826314898580176896 |
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| author | Downton, P Dickson, SH Ray, DW Bechtold, DA Gibbs, JE |
| author_facet | Downton, P Dickson, SH Ray, DW Bechtold, DA Gibbs, JE |
| author_sort | Downton, P |
| collection | OXFORD |
| 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. |
| first_indexed | 2024-09-25T04:13:34Z |
| format | Journal article |
| id | oxford-uuid:396502ed-2918-4da3-a05c-ca1cb77cc5fb |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:14:45Z |
| publishDate | 2024 |
| publisher | The Royal Society |
| record_format | dspace |
| spelling | oxford-uuid:396502ed-2918-4da3-a05c-ca1cb77cc5fb2024-10-16T09:44:30ZFibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:396502ed-2918-4da3-a05c-ca1cb77cc5fbEnglishJisc Publications RouterThe Royal Society2024Downton, PDickson, SHRay, DWBechtold, DAGibbs, JERheumatoid 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. |
| spellingShingle | Downton, P Dickson, SH Ray, DW Bechtold, DA Gibbs, JE Fibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritis |
| title | Fibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritis |
| title_full | Fibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritis |
| title_fullStr | Fibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritis |
| title_full_unstemmed | Fibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritis |
| title_short | Fibroblast-like synoviocytes orchestrate daily rhythmic inflammation in arthritis |
| title_sort | fibroblast like synoviocytes orchestrate daily rhythmic inflammation in arthritis |
| work_keys_str_mv | AT downtonp fibroblastlikesynoviocytesorchestratedailyrhythmicinflammationinarthritis AT dicksonsh fibroblastlikesynoviocytesorchestratedailyrhythmicinflammationinarthritis AT raydw fibroblastlikesynoviocytesorchestratedailyrhythmicinflammationinarthritis AT bechtoldda fibroblastlikesynoviocytesorchestratedailyrhythmicinflammationinarthritis AT gibbsje fibroblastlikesynoviocytesorchestratedailyrhythmicinflammationinarthritis |