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By
From the * Maxillofacial Surgery Research Unit, Eastman Dental Institute, University College
London, London WC1X 8LD, 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.
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
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