A Bmpr1a soluble receptor construct increases tibial and trabecular bone volume in vivo

Abstract

Event Abstract Back to Event A Bmpr1a soluble receptor construct increases tibial and trabecular bone volume in vivo MA Baud'Huin1*, D Lath1, AD Chantry1, J Seehra2, RS Pearsall2, I Bellantuono1 and PI Croucher1 1 University of Sheffield, Mellanby Centre for Bone Research, Faculty of Medicine Dentistry and Health, United Kingdom 2 Acceleron Pharma, United States Bone morphogenic proteins (BMPs) are members of the TGF-b superfamily and act as pleiotropic regulators of skeletal organogenesis and bone homeostasis. BMP signalling is regulated through a heterotetrameric receptor complex composed of both a BMP type I serine/threonine kinase receptor (including the BMP Receptor1A (BMPR1A), the BMP Receptor1B and the Activin Type Receptor 1) and a type II serine/threonine kinase kinase receptor. The various combinations of the Type I and Type II receptors results in modulation of ligand signalling on target organs. This has made defining the relative contribution of individual BMPs and TGF-b superfamily members regulating bone mass difficult. Therefore, the aim of this study was to determine the role of one component of this system, the BMPR1A, in regulating bone mass in vivo. {BR}The extracellular domain of the murine BMPR1A fused to a murine Fc-domain was expressed in CHO cells to create a soluble BMPR1A fusion protein (RAP-661). C57BL/6 male mice were treated with RAP-661 (10mg/kg, twice a week, i.p.), or vehicle (PBS), and groups (n=6 to 9) sacrificed after 3, 7, 14 or 28 days. The tibia and vertebrae (L4) were analysed by microCT and processed for bone histomorphometry. Trabecular bone volume in the tibia was increased by 38%, 33% and 51% after 7, 14 and 28 days, respectively, in RAP661-treated mice compared to control (p<0.05 in each case). RAP-661 also increased trabecular bone volume in vertebrae by 18%, 34% and 55% at 7, 14 and 28 days (p<0.05 in each case). This was associated with an increase in trabecular number and trabecular thickness in both tibia (p<0.05) and vertebra at 7, 14, 28 days (p<0.05 and p<0.05). Histomorphometric analysis demonstrated an increase in osteoblast number at day 7 (p<0.05). There were no difference between RAP-661 treated mice and mice treated with vehicle at day 14 and 28. In contrast, osteoclasts number was not different from control at days 3 but were significantly decreased at day 14 and 28 (p<0.01).{BR}These data demonstrate that inhibiting ligands that signalling through BMPR1A is able to increase bone mass and could offer a therapeutic approach to increasing bone mass. Keywords: Bones, Bone Research Conference: 2011 joint meeting of the Bone Research Society & the British Orthopaedic Research Society, Cambridge, United Kingdom, 27 Jun - 29 Jun, 2011. Presentation Type: Oral Topic: Abstracts Citation: Baud'Huin M, Lath D, Chantry A, Seehra J, Pearsall R, Bellantuono I and Croucher P (2011). A Bmpr1a soluble receptor construct increases tibial and trabecular bone volume in vivo. Front. Endocrinol. Conference Abstract: 2011 joint meeting of the Bone Research Society & the British Orthopaedic Research Society. doi: 10.3389/conf.fendo.2011.02.00004 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Sep 2011; Published Online: 30 Sep 2011. * Correspondence: Dr. MA Baud'Huin, University of Sheffield, Mellanby Centre for Bone Research, Faculty of Medicine Dentistry and Health, Sheffield, United Kingdom, M.Baudhuin@sheffield.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers MA Baud'Huin D Lath AD Chantry J Seehra RS Pearsall I Bellantuono PI Croucher Google MA Baud'Huin D Lath AD Chantry J Seehra RS Pearsall I Bellantuono PI Croucher Google Scholar MA Baud'Huin D Lath AD Chantry J Seehra RS Pearsall I Bellantuono PI Croucher PubMed MA Baud'Huin D Lath AD Chantry J Seehra RS Pearsall I Bellantuono PI Croucher Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.