Pharmacological topics of bone metabolism: antiresorptive microbial compounds that inhibit osteoclast differentiation, function, and survival.
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.
Woo
Je-Tae
JT
Department of Biological Chemistry, Chubu University, Matsumoto, Kasugai, Japan. jwoo@isc.chubu.ac.jp
Yonezawa
Takayuki
T
Cha
Byung-Yoon
BY
Teruya
Toshiaki
T
Nagai
Kazuo
K
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
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