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.
Mycobacterium tuberculosis Chaperonin 10 Stimulates Bone Resorption: A Potential Contributory Factor in Pott's Disease
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: [email protected]
Abbreviations used in this paper: cpn, chaperonin; LAM, lipoarabinomannan; Mt, Mycobacterium tuberculosis.
Sajeda Meghji, Peter A. White, Sean P. Nair, Krisanavane Reddi, Kyle Heron, Brian Henderson, Andrea Zaliani, Gianluca Fossati, Paolo Mascagni, John F. Hunt, Michael M. Roberts, Anthony R.M. Coates; Mycobacterium tuberculosis Chaperonin 10 Stimulates Bone Resorption: A Potential Contributory Factor in Pott's Disease . J Exp Med 20 October 1997; 186 (8): 1241–1246. doi: https://doi.org/10.1084/jem.186.8.1241
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