Τίτλος:
Epigenetically-driven anatomical diversity of synovial fibroblasts guides joint-specific fibroblast functions
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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 responsiveness 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. © The Author(s) 2017.
Συγγραφείς:
Frank-Bertoncelj, M.
Trenkmann, M.
Klein, K.
Karouzakis, E.
Rehrauer, H.
Bratus, A.
Kolling, C.
Armaka, M.
Filer, A.
Michel, B.A.
Gay, R.E.
Buckley, C.D.
Kollias, G.
Gay, S.
Ospelt, C.
Περιοδικό:
Nature Communications
Εκδότης:
Nature Publishing Group
Λέξεις-κλειδιά:
collagenase 3; HAND2 protein; HOTAIR protein; HOTTIP protein; HOXA11 AS1 protein; HOXA11 AS2 protein; HOXA11 protein; HOXA13 protein; HOXD10 protein; HOXD13 protein; interleukin 1 receptor; interleukin 18; interleukin 27; interleukin 34; interstitial collagenase; ITG2B protein; ITGA8 protein; long untranslated RNA; MEIS1 protein; MEIS2 protein; microRNA; protein; ROR2 protein; secreted frizzled related protein 4; stromal cell derived factor 1; transcription factor T bet; transcription factor TBX5; transcriptome; tumor necrosis factor; unclassified drug; untranslated RNA; homeodomain protein; oncoprotein; TLX1 protein, human, anatomy; gene expression; methylation; pathology; phenotype; protein; rodent, anatomical variation; animal experiment; animal model; arthritis; Article; biodiversity; cell proliferation; controlled study; disease severity; DNA methylation; elbow; epigenetics; fibroblast; gene expression; hand joint; hip; histone modification; Hox gene; human; human tissue; joint function; knee; microenvironment; mouse; nonhuman; phenotypic variation; shoulder; stroma; synovial fibroblast; synovial fluid; synovium; transcriptomics; animal; C57BL mouse; cell culture; cytology; fibroblast; gene expression profiling; genetics; histone code; joint; metabolism; osteoarthritis; pathology; rheumatoid arthritis; synovium; transgenic mouse, Animals; Arthritis, Rheumatoid; Cells, Cultured; DNA Methylation; Epigenomics; Fibroblasts; Gene Expression Profiling; Histone Code; Homeodomain Proteins; Humans; Joints; Mice, Inbred C57BL; Mice, Transgenic; Osteoarthritis; Proto-Oncogene Proteins; Synovial Membrane
