Epigenetically-driven anatomical diversity of
Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions.
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.
Many forms of chronic arthritis occur with a specific pattern of joint affection. Rheumatoid arthritis for instance typically evolves in the small joints of the hands and feet and later spreads to elbows and knees. In this study, we could show that joint tissues and synovial fibroblasts, the main resident cells in the joint substantially differ between different joint regions. Epigenetic mechanisms such as DNA methylation and histone modifications regulate joint-specific HOX gene expression that is established during embryonic development. Anatomical transcriptional diversity translates into joint-specific synovial fibroblast phenotypes with distinct adhesive, proliferative, chemotactic and matrix-degrading characteristics and differential responsiveness to TNF. Our findings indicate that the microenvironment in each joint, in health and disease, is quite unique. The differences between the joints could define the susceptibility of certain joints to develop disease and the response to anti-inflammatory treatments.
Key idea/result:
Each joint has a specific molecular microenvironment sustained by synovial fibroblasts that might influence susceptibility to disease and response to treatment
Author:
Mojca Frank-Bertoncelj is a senior postdoctoral scientist at the Centre of Experimental Rheumatology, University Hospital Zurich since 2012. Her major scientific interest is the association of arthritis with developmental joint biology and anatomic diversity of stromal cells.