The Escherichia coli chaperonin 60 (groEL) is a potent stimulator of osteoclast formation.
Chaperonins (cpns) are intracellular oligomeric protein complexes that fold and refold proteins in a catalytic manner and aid in the transmembrane transport of cellular proteins. We reported previously that the lipopolysaccharide-free recombinant cpn60 of Escherichia coli (groEL) is able to stimulate the breakdown of murine calvarial bone in culture and showed that such resorption is potently inhibited by an inhibitor of the enzyme cyclo-oxygenase and to a lesser extent by inhibitors of 5-lipoxygenase. In this study, we have investigated the effects of groEL on the resorptive activity and formation of osteoclasts in culture. In low density, osteoclast-containing cultures from neonatal rats incubated for 24 or 96 h on dentine discs, groEL (1-1000 ng/ml) stimulated resorption pit formation up to 4-fold, but this effect was essentially dependent on cell number. Using 12-day cultures of mouse bone marrow to assess osteoclast recruitment, groEL (1-1000 ng/ml) caused a dramatic dose-dependent stimulation of the formation of tartrate-resistant acid phosphatase-positive multinucleated cells and the resorption of the dentine on which bone marrow cells were cultured. Osteoclast formation elicited by groEL was almost completely abolished by indomethacin, an inhibitor of cyclo-oxygenase, but was unaffected by inhibitors of 5-lipoxygenase, suggesting that prostaglandins but not leukotrienes may mediate the action of groEL on osteoclastogenesis. It is possible that bacterial cpn60s such as groEL may play a role in the osteolysis associated with bone infections. Whether endogenous ("self") chaperonins have a role in other bone loss disorders, such as osteoporosis, is an intriguing possibility.
Maxillofacial Surgery Research Unit, Eastman Dental Institute, University College London, United Kingdom.
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K
Reddi
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Meghji
S P
SP
Nair
T R
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Arnett
A D
AD
Miller
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Preuss
M
M
Wilson
B
B
Henderson
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Hill
D000135:Acid Phosphatase; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D001862:Bone Resorption / Q000139:chemically induced; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli; D015726:Giant Cells / Q000166:cytology / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D000071681:Tartrate-Resistant Acid Phosphatase
D018834:Chaperonin 60; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D016859:Lipoxygenase Inhibitors; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D007213:Indomethacin