Author/Editor		Frank Bertoncelj, Mojca; Trenkmann, Michelle; Klein, Kerstin; Karouzakis, Emmanuel; Rehrauer, Hubert; Bratus, Anna; Kolling, Christoph; Armaka, Maria; Filer, Andrew; Michel, Beat A.
Title		Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast function
Type		članek
Vol. and No.		, št. Vol. 8
Publication year		2017
Volume		str. 1-14
ISSN		2041-1723 - Nature communications
Language		eng
Abstract		A number of human diseases, such as arthritis and atherosclerosis, include characteristic pathology in specific anatomical locations. Here we show transcriptomic differences in synovial fibroblasts from different joint locations and that HOX gene signatures reflect the joint-specific origins of mouse and human synovial fibroblasts and synovial tissues. Alongside DNA methylation and histone modifications, bromodomain and extra-terminal reader proteins regulate joint-specific HOX gene expression. Anatomical transcriptional diversity translates into joint-specific synovial fibroblast phenotypes with distinct adhesive, proliferative, chemotactic and matrix-degrading characteristics and differential responsive- ness to TNF, creating a unique microenvironment in each joint. These findings indicate that local stroma might control positional disease patterns not only in arthritis but in any disease with a prominent stromal component.
Keywords		synovial fibroblasts anatomical diversity arthritis and atherosclerosis sinovialni fibroblastomi anatomska raznolikost artritis in ateroskleroza