ArticleProceedings of the National Academy of Sciences of the United States of America2006
Reveromycin A, an agent for osteoporosis, inhibits bone resorption by inducing apoptosis specifically in osteoclasts.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 83 citations in OpenAlex.
- Biosynthesis of reveromycin derivatives by altering the regioselectivity of cytochrome P450revI.Chemical science · 2025Article
- Chemical biology research in RIKEN NPDepo aimed at agricultural applications.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025Review
- The mARS complex: a critical mediator of immune regulation and homeostasis.Frontiers in immunology · 2024Review
- Optimized submerged batch fermentation for metabolic switching inFrontiers in microbiology · 2024Article
- An asymmetric structure of bacterial TrpRS supports the half-of-the-sites catalytic mechanism and facilitates antimicrobial screening.Nucleic acids research · 2023Article
- Studies on Streptomyces sp. SN-593: reveromycin biosynthesis, β-carboline biomediator activating LuxR family regulator, and construction of terpenoid biosynthetic platform.The Journal of antibiotics · 2022Review
- Benzofuran pyran hybrid prevents glucocorticoid induced osteoporosis in mice via modulation of canonical Wnt/β-catenin signaling.Apoptosis : an international journal on programmed cell death · 2022Article
- Review
- Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease.International journal of molecular sciences · 2021Review
- Reveromycin A, a novel acid-seeking agent, ameliorates bone destruction and tumor growth in multiple myeloma.Haematologica · 2021Article
- Inhibitory mechanism of reveromycin A at the tRNA binding site of a class I synthetase.Nature communications · 2021Article
- A Quick Guide to Small-Molecule Inhibitors of Eukaryotic Protein Synthesis.Biochemistry. Biokhimiia · 2020Review
- β-carboline chemical signals induce reveromycin production through a LuxR family regulator in Streptomyces sp. SN-593.Scientific reports · 2020Article
- Non-canonical Wnt signals regulate cytoskeletal remodeling in osteoclasts.Cellular and molecular life sciences : CMLS · 2018Review
- Kinanthraquinone, a new anthraquinone carboxamide isolated from Streptomyces reveromyceticus SN-593-44.The Journal of antibiotics · 2018Article
- Reveromycins A and B fromFrontiers in microbiology · 2017Article
- Proteomic profiling reveals that collismycin A is an iron chelator.Scientific reports · 2016Article
- Chemical and biological studies of reveromycin A.The Journal of antibiotics · 2016Review
- Reveromycin A Administration Prevents Alveolar Bone Loss in Osteoprotegerin Knockout Mice with Periodontal Disease.Scientific reports · 2015Article
- Identification of Middle Chain Fatty Acyl-CoA Ligase Responsible for the Biosynthesis of 2-Alkylmalonyl-CoAs for Polyketide Extender Unit.The Journal of biological chemistry · 2015Article
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mature bone-resorbing osteoclasts (OCs) mediate excessive bone loss seen in several bone disorders, including osteoporosis. Here, we showed that reveromycin A (RM-A), a small natural product with three carboxylic groups in its structure, induced apoptosis specifically in OCs, but not in OC progenitors, nonfunctional osteoclasts, or osteoblasts. RM-A inhibited protein synthesis in OCs by selectively blocking enzymatic activity of isoleucyl-tRNA synthetase. The proapoptotic effect of RM-A was inhibited by neutralization or disruption of the acidic microenvironment, a prominent characteristic of OCs. RM-A was incorporated in OCs but not in nonfunctional osteoclasts and OC progenitors in neutral culture medium. Effects of RM-A on OC apoptosis increased under acidic culture conditions. RM-A not only was incorporated, but also induced apoptosis in OC progenitors in acidic culture medium. RM-A inhibited osteoclastic pit formation, decreased prelabeled (45)Ca release in organ cultures, and antagonized increased bone resorption in ovariectomized mice. These results suggested that preventive effects of RM-A on bone resorption in vitro and in vivo were caused by apoptosis through inhibition of isoleucyl-tRNA synthetase in OCs and that specific sensitivity of OCs to RM-A was due to the acidic microenvironment, which increased cell permeability of RM-A by suppressing dissociation of protons from carboxylic acid moieties, making them less polar. This unique mechanism suggested that RM-A might represent a type of therapeutic agent for treating bone disorders associated with increased bone loss.
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