MYCOBACTERIUM-TUBERCULOSIS CHAPERONIN-10 STIMULATES BONE-RESORPTION -A POTENTIAL CONTRIBUTORY FACTOR IN POTTS-DISEASE

Poet's disease (spinal tuberculosis), a condition characterized by mas sive resorption of the spinal vertebrae, is one of the most striking p athologies resulting from local infection with Mycobacterium tuberculo sis (Mt; Boachie-Adjei, O., and R.G. Squillante. 1996. Orthop. Clin. N orth Am. 27:95-103). The pathogenesis of Pott's disease is not establi shed. 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) chap eronin (cpn) 10, is responsible for the osteolytic activity of this ba cterium. Recombinant Mt cpn10 is a potent stimulator of bone resorptio n in bone explant cultures and induces osteoclast recruitment, while i nhibiting the proliferation of an osteoblast bone-forming cell line. F urthermore, we have found that synthetic peptides corresponding to seq uences within the flexible loop and sequence 65-70 of Mt cpn10 may com prise a single conformational unit which encompasses its potent bone-r esorbing activity. Our findings suggest that Mt cpn10 may be a valuabl e pharmacological target for the clinical therapy of vertebral tubercu losis and possibly other bone diseases.