RANKL increases the level of Mcl-1 in osteoclasts and reduces bisphosphonate-induced osteoclast apoptosis in vitro 英文参考文献.docVIP

Available online /content/11/2/R58 Research article Open Access Vol 11 No 2 RANKL increases the level of Mcl-1 in osteoclasts and reduces bisphosphonate-induced osteoclast apoptosis in vitro Karen A Sutherland*, Helena L Rogers*, Denise Tosh and Michael J Rogers Bone Musculoskeletal Research Programme, School of Medicine Dentistry, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK * Contributed equally Corresponding author: Michael J Rogers, m.j.rogers@abdn.ac.uk Received: 25 Jun 2008 Revisions requested: 31 Jul 2008 Revisions received: 8 Apr 2009 Accepted: 30 Apr 2009 Published: 30 Apr 2009 Arthritis Research Therapy 2009, 11:R58 (doi:10.1186/ar2681) This article is online at: /content/11/2/R58 ? 2009 Sutherland et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Introduction Bisphosphonates are the most widely used class of drug for inhibiting osteoclast-mediated bone loss, but their effectiveness at preventing joint destruction in rheumatoid arthritis has generally been disappointing. We examined whether the ability of bisphosphonates to induce osteoclast apoptosis and inhibit bone resorption in vitro is influenced by the cytokine receptor activator of nuclear factor-kappa B ligand (RANKL), an important mediator of inflammation-induced bone loss. Results RANKL significantly attenuated the ability of both clodronate and alendronate to induce osteoclast apoptosis and inhibit bone resorption. Treatment of rabbit osteoclasts with RANKL was associated with an increase in the anti-apoptotic protein Mcl-1 but not Bcl-2. A role for Mcl-1 in osteoclast survival was suggested using osteoclasts generated from mo