The Journal of Experimental Medicine
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article
Right arrow Full Text
Right arrow Full Text (PDF, 179K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Meghji, S.
Right arrow Articles by Coates, A. R.M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Meghji, S.
Right arrow Articles by Coates, A. R.M.
Social Bookmarking
 Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/1997/10/1241/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 8, October 20, 1997 1241-1246


Articles

Mycobacterium tuberculosis Chaperonin 10 Stimulates Bone Resorption: A Potential Contributory Factor in Pott's Disease

Sajeda Meghji*, Peter A. White*, Sean P. Nair*, Krisanavane Reddi*, Kyle Heron*, Brian Henderson*, Andrea Zaliani{ddagger}, Gianluca Fossati§, Paolo Mascagni{ddagger}, John F. Hunt||, Michael M. Roberts, and Anthony R.M. Coates

From the * Maxillofacial Surgery Research Unit, Eastman Dental Institute, University College London, London WC1X 8LD, United Kingdom; {ddagger} Italfarmaco SpA, Centro Richerche, 20092 Cinisello B (MI), Italy; § Molecular Immunology Division, National Institute for Medical Research, London NW7 1AA, United Kingdom; || Howard Hughes Medical Institute, The University of Texas, Southwestern Medical Center, Dallas, Texas 75235; and Division of Molecular Microbiology, St. George's Hospital Medical School, London SW17 0RE, United Kingdom

Pott's disease (spinal tuberculosis), a condition characterized by massive resorption of the spinal vertebrae, is one of the most striking pathologies resulting from local infection with Mycobacterium tuberculosis (Mt; Boachie-Adjei, O., and R.G. Squillante. 1996. Orthop. Clin. North Am. 27:95–103). The pathogenesis of Pott's disease is not established. Here we report for the first time that a protein, identified by a monoclonal antibody to be the Mt heat shock protein (Baird, P.N., L.M. Hall, and A.R.M. Coates. 1989. J. Gen. Microbiol. 135:931–939) chaperonin (cpn) 10, is responsible for the osteolytic activity of this bacterium. Recombinant Mt cpn10 is a potent stimulator of bone resorption in bone explant cultures and induces osteoclast recruitment, while inhibiting the proliferation of an osteoblast bone–forming cell line. Furthermore, we have found that synthetic peptides corresponding to sequences within the flexible loop and sequence 65–70 of Mt cpn10 may comprise a single conformational unit which encompasses its potent bone-resorbing activity. Our findings suggest that Mt cpn10 may be a valuable pharmacological target for the clinical therapy of vertebral tuberculosis and possibly other bone diseases.


Address correspondence to Dr. Michael Mark Roberts, RM 1.241A, Jenner Wing, Level 1, Division of Molecular Microbiology, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, United Kingdom. Phone: 44-181-725-5722; FAX: 44-181-672-0234; E-mail: m.roberts{at}sghms.ac.uk

1 Abbreviations used in this paper: cpn, chaperonin; LAM, lipoarabinomannan; Mt, Mycobacterium tuberculosis.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS