Mycobacterium tuberculosis chaperonin 10 stimulates bone resorption: a potential contributory factor in Pott's disease.
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.
Meghji
S
S
Maxillofacial Surgery Research Unit, Eastman Dental Institute, University College London, United Kingdom.
White
P A
PA
Nair
S P
SP
Reddi
K
K
Heron
K
K
Henderson
B
B
Zaliani
A
A
Fossati
G
G
Mascagni
P
P
Hunt
J F
JF
Roberts
M M
MM
Coates
A R
AR
D000595:Amino Acid Sequence; D000818:Animals; D001862:Bone Resorption / Q000378:metabolism* / Q000382:microbiology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D018835:Chaperonin 10 / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000502:physiology*; D009924:Organ Culture Techniques; D010006:Osteoblasts; D010446:Peptide Fragments / Q000494:pharmacology; D010449:Peptide Mapping; D011994:Recombinant Proteins / Q000494:pharmacology; D012886:Skull; D013010:Sonication; D014399:Tuberculosis, Spinal / Q000378:metabolism* / Q000382:microbiology*
D018835:Chaperonin 10; D006131:Growth Inhibitors; D010446:Peptide Fragments; D011994:Recombinant Proteins; D002118:Calcium