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Human chaperonin 60 (Hsp60) stimulates bone resorption: structure/function relationships.

S Meghji1, M Lillicrap, M Maguire

  • 1Cellular Microbiology Research Group, Eastman Dental Institute, University College London, 256 Gray's Inn Road, London WC1X 8LD, UK.

Bone
|September 19, 2003
PubMed
Summary
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Human heat shock protein 60 (Hsp60) potently stimulates bone resorption, independent of its cytokine activity. The C-terminal region of Hsp60 appears crucial for this osteolytic function, suggesting a role in bone remodeling.

Area of Science:

  • Molecular biology
  • Immunology
  • Bone biology

Background:

  • Molecular chaperones like chaperonin 60 (Hsp60) exhibit cell-cell signaling and cytokine induction.
  • Previous studies indicated bacterial Hsp60 from Gram-negative bacteria, but not mycobacteria, can resorb bone.
  • Hsp60 is found in human blood at levels potentially activating bone cells.

Purpose of the Study:

  • To investigate the bone resorbing activity of human recombinant Hsp60.
  • To identify the active domain of Hsp60 responsible for osteolytic activity.
  • To explore the role of Hsp60 in bone remodeling.

Main Methods:

  • Assessing the effect of lipopolysaccharide-low human recombinant Hsp60 on murine calvarial bone resorption.
  • Evaluating the inhibitory effects of indomethacin, interleukin-1 receptor antagonist, osteoprotegerin, and 5-lipoxygenase inhibitors on Hsp60-induced bone resorption.

Related Experiment Videos

  • Analyzing the bone resorbing activity of various Hsp60 N-terminal and C-terminal truncation mutants.

    • Main Results:

    • Human recombinant Hsp60 is a potent stimulator of murine calvarial bone resorption, with weaker cytokine-inducing capacity.
    • Osteolytic activity of Hsp60 was significantly inhibited by indomethacin, IL-1 receptor antagonist, and osteoprotegerin.
    • N-terminal Hsp60 mutants retained bone resorbing activity, while a C-terminal mutant was inactive, localizing the active domain to residues 466-573.

    Conclusions:

    • The C-terminal domain of Hsp60 (residues 466-573) is essential for its bone resorbing activity.
    • Hsp60's osteolytic function is distinct from its cytokine-inducing activity.
    • Elevated Hsp60 levels in the general population suggest a potential role in physiological bone remodeling.