Pharmacological topics of bone metabolism: antiresorptive microbial compounds that inhibit osteoclast differentiation, function, and survival

J Pharmacol Sci. 2008 Apr;106(4):547-54. doi: 10.1254/jphs.fm0070288.

Abstract

The mass and function of bones depends on the maintenance of a complicated balance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Osteoporosis typically reflects an imbalance in skeletal turnover, such that bone resorption exceeds bone formation. Osteoclasts are target cells for anti-osteoporosis therapies. To discover new types of antiresorptive agents, we screened for natural compounds that regulate osteoclast differentiation, function, and survival. As a result, we identified reveromycin A, destruxins, mevastatin, FK506, cyclosporin A, prodigiosins, concanamycins, and symbioimine among microbial natural compounds. In this review, we discuss the mechanisms of action of these compounds on osteoclasts.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Bacteria / chemistry*
  • Bone Density Conservation Agents / isolation & purification
  • Bone Density Conservation Agents / pharmacology*
  • Bone Density Conservation Agents / therapeutic use
  • Bone Resorption / metabolism
  • Bone Resorption / pathology
  • Bone Resorption / prevention & control*
  • Cell Differentiation / drug effects*
  • Cell Survival / drug effects
  • Cyclosporine / pharmacology
  • Depsipeptides / pharmacology
  • Fungi / chemistry*
  • Heterocyclic Compounds, 3-Ring / pharmacology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Lovastatin / analogs & derivatives
  • Lovastatin / pharmacology
  • Osteoclasts / drug effects*
  • Osteoclasts / metabolism
  • Osteoclasts / pathology
  • Prodigiosin / pharmacology
  • Pyrans / pharmacology
  • Spiro Compounds / pharmacology
  • Tacrolimus / pharmacology

Substances

  • Bone Density Conservation Agents
  • Depsipeptides
  • Heterocyclic Compounds, 3-Ring
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrans
  • Spiro Compounds
  • symbioimine
  • reveromycin A
  • mevastatin
  • Cyclosporine
  • Lovastatin
  • Prodigiosin
  • Tacrolimus