WNT5A is induced by inflammatory mediators in bone marrow stromal cells and regulates cytokine and chemokine production

• DOI: 10.1002/jbmr.1488
• Publication Date: 2011-12-08T15:56:19Z
• Authors: Martina Rauner; Nicola Stein; Maria Winzer; Claudia Goettsch; Jochen Zwerina; Georg Schett; Jörg HW Distler; Joachim Albers; Jochen Schulze; Thorsten Schinke; Martin Bornhäuser; Uwe Platzbecker; Lorenz C Hofbauer
• Keywords: Adult; Lipopolysaccharides; Male; 0303 health sciences; Tumor Necrosis Factor-alpha; Bone Marrow Cells; Cell Separation; Middle Aged; 3. Good health; Arthritis, Rheumatoid; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Cell Movement; Proto-Oncogene Proteins; Animals; Cytokines; Humans; Female; Chemokines; Inflammation Mediators; Stromal Cells; Cells, Cultured

Abstract WNT5A has recently been implicated in inflammatory processes, but its role as a bone marrow stromal cell (BMSC)–derived mediator of joint inflammation arthritis is unclear. Here, we investigated whether stimuli induce BMSC to control responses. levels were determined human after stimulation with lipopolysaccharide (LPS) or tumor necrosis factor α (TNF-α,) and synovial cells tissue patients rheumatoid (RA) TNF-α transgenic (hTNFtg) mice. A microarray analysis WNT5A-treated murine osteoblasts was performed using Affymetrix gene chips. The regulation cytokine/chemokine expression confirmed by qPCR, ELISA, Luminex technology knockdown. Relevant signaling pathways identified specific inhibitors. Migration MACS-purified T lymphocytes monocytes assessed the FluoroBlok system. increased threefold LPS TNF-α. Synovial fibroblasts from RA showed twofold increase compared cells, highly induced hTNFtg Microarray cytokines chemokines targets. induction IL-1β, IL-6, CCL2, CCL5, CXCL1, CXCL5 depended on activation NF-κB, mitogen-activated protein (MAPK), Akt pathways. Accordingly, knockdown markedly reduced basal LPS-induced production. Finally, migration toward supernatant 25% 20%, respectively. This study underlines critical BMSC-derived processes suggests participation pathogenesis RA. © 2012 American Society for Bone Mineral Research.