Joint specific phenotypes of synovial fibroblasts
We have shown that synovial fibroblasts isolated from different joints substantially differ in gene expression and functional properties such as chemotactic and adhesive activity. These joint-specific phenotypes of synovial fibroblasts are reflected in joint-specific epigenetic landscapes, in particular regulating the expression of genes that are involved in the embryonic development of the respective joint regions (e.g. HOX genes). Based on these data, we hypothesize that the joint-specific phenotypes shaped during embryonic development and maintained during adult life, significantly contribute to the pathognomic patterns of joint affection in chronic inflammatory arthritis such as RA. Thus, we analyse the joint-specific composition of synovial tissues in health and disease, the functions of key regulators of joint-specific gene expression (e.g. long non-coding RNA, transcription factors) and joint-specific differences in response to inflammatory stimuli and therapy.
Researcher in charge
- Prof Christopher Buckley, Dr Andrew Filer, Institute of Inflammation and Ageing, University of Birmingham, UK
- Prof Stephen Eyre, Arthritis Research UK Centre for Genetics and Genomics, University of Manchester, UK
- Prof George Kollias, Dr Marietta Armaka, Biomedical Sciences Research Center 'Alexander Fleming', Athens, Greece
- Frank-Bertoncelj M, Trenkmann M, Klein K, Karouzakis E, Rehrauer H, Bratus A, Kolling C, Armaka M, Filer A, Michel BA, Gay RE, Buckley CD, Kollias G, Gay S, Ospelt C. Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions. Nat. Commun. 8, 14852 doi: 10.1038/ncomms14852 (2017)
- Ospelt C, Frank-Bertoncelj M. Why location matters – site-specific factors in rheumatic diseases. Nat Rev Rheumatol. 2017 Jul;13(7):433-442. doi: 10.1038/nrrheum.2017.96.