Role of the A20 TRAF6 Axis in Lipopolysaccharide mediated Osteoclastogenesis英文文献.pdfVIP

THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 286, NO. 5, pp. 3242–3249, February 4, 2011 © 2011 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in the U.S.A. Role of the A20-TRAF6 Axis in Lipopolysaccharide-mediated Osteoclastogenesis* Received for publication, June 1, 2010, and in revised form, October 22, 2010 Published, JBC Papers in Press, December 2, 2010, DOI 10.1074/jbc.M110.150300 ‡§1 § ‡ Guillaume Mabilleau , Daniel Chappard , and Afsie Sabokbar From the ‡Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, § OX3 7LD Oxford, United Kingdom and INSERM, U922, Laboratory of Histology and Embryology of Angers, Faculty of Medicine, University of Angers, 49933 Angers Cedex 09, France Bacterial lipopolysaccharide (LPS) has long been suggested oclast precursors (8, 9). One of the crucial steps, in the down- as a potent inducer of bone loss in vivo despite controversial stream signaling pathway of RANK/RANKL interaction is the effects on osteoclast precursors. Recently, the role of the deu- recruitment of TNF receptor-associated factors (TRAFs) to biquitinating protease A20 in regulating the LPS response in the intracellular tail of RANK (10, 11). Among the different various organs was reported. In the present study, we investi- TRAFs binding RANK, TRAF6 is considered essential for os- gated whether A20 is expressed in osteoclast cultures in re- teoclast function because TRAF6 knock-out animals exhibit sponse to RANKL or LPS and whether this protein plays a role