title: Pharmacological topics of bone metabolism: antiresorptive microbial compounds that inhibit osteoclast differentiation, function, and survival.
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.
authors.affiliation: Department of Biological Chemistry, Chubu University, Matsumoto, Kasugai, Japan. jwoo@isc.chubu.ac.jp
authors.forename: Je-Tae
authors.initials: JT
authors.lastname: Woo
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yonezawa
authors.forename: Byung-Yoon
authors.initials: BY
authors.lastname: Cha
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Teruya
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nagai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001419:Bacteria / Q000737:chemistry*; D050071:Bone Density Conservation Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D047630:Depsipeptides / Q000494:pharmacology; D005658:Fungi / Q000737:chemistry*; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D008148:Lovastatin / Q000031:analogs & derivatives / Q000494:pharmacology; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011353:Prodigiosin / Q000494:pharmacology; D011714:Pyrans / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D050071:Bone Density Conservation Agents; D047630:Depsipeptides; D006575:Heterocyclic Compounds, 3-Ring; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011714:Pyrans; D013141:Spiro Compounds; C505668:symbioimine; C068098:reveromycin A; C012258:mevastatin; D016572:Cyclosporine; D008148:Lovastatin; D011353:Prodigiosin; D016559:Tacrolimus