Autotaxin expression from synovial fibroblasts is essential for the pathogenesis of modeled arthritis

• DOI: 10.1084/jem.20112012
• Publication Date: 2012-04-10T00:47:16Z
• Authors: Ioanna Nikitopoulou; Nikos Oikonomou; Emmanuel Karouzakis; Ioanna Sevastou; Nefeli Nikolaidou...; Zhenwen Zhao; Vassilis Mersinias; Maria Armaka; Yan Xu; Masayuki Masu; Gordon B. Mills; Steffen Gay; George Kollias; Vassilis Aidinis
• Keywords: Autotaxin; Proinflammatory cytokine; Pathogenesis

Rheumatoid arthritis is a destructive arthropathy characterized by chronic synovial inflammation that imposes substantial socioeconomic burden. Under the influence of proinflammatory milieu, fibroblasts (SFs), main effector cells in disease pathogenesis, become activated and hyperplastic, releasing factors tissue-remodeling enzymes. This study shows arthritic SFs from human patients animal models express significant quantities autotaxin (ATX; ENPP2), lysophospholipase D catalyzes conversion lysophosphatidylcholine to lysophosphatidic acid (LPA). ATX expression was induced TNF, LPA SF activation functions synergy with TNF. Conditional genetic ablation mesenchymal cells, including SFs, resulted attenuation arthritis, establishing ATX/LPA axis as novel player pathogenesis promising therapeutic target.