Brief Definit ive Report

Rheumatoid arthritis (RA) pathogenesis is characterized by a hyperplastic synovial mem-brane caused by synovial cell proliferation and infiltration by inflammatory cells (Müller-Ladner et al., 2005). Synovial fibroblasts (SFs) are among the dominant cell types of the ar-thritic synovium that under the influence of the inflammatory milieu and/or possible epi-genetic changes become activated and hyper-plastic, releasing several effector signals including proinflammatory factors and tissue-remodeling enzymes (Karouzakis et al., 2009). Autotaxin (ATX) is a secreted lysophos-pholipase D, widely present in biological fluids, catalyzing the conversion of lysophosphatidyl-choline (LPC) to lysophosphatidic acid (LPA; Aoki, 2004; van Meeteren and Moolenaar, 2007). LPA evokes growth factor–like responses in almost all cell types, including cell growth, survival, differentiation, and motility (Mills and Moolenaar, 2003). The wide variety of LPA effector functions is attributed to at least five G-protein–coupled LPA receptors (LPARs) with overlapping specificities and widespread distribution (Choi et al., 2008). Increased ATX expression has been detected in a large variety of cancers (van Meeteren and Moolenaar, 2007); in this study, substantial ATX expression is detected from SFs in arthritic joints of animal models and human patients. Conditional genetic ablation of ATX in SFs (and other mesenchymal cells) is shown to attenuate disease pathogenesis, attributed to diminished LPA signaling to SFs