ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2018
Folliculin Regulates Osteoclastogenesis Through Metabolic Regulation.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 27 citations in OpenAlex.
- Identification and Validation of programmed cell death-related biomarkers in Osteoarthritis and an Exploratory Pan-Cancer Analysis: SHARPIN as a Potential Biomarker.Clinical rheumatology · 2026Article
- Promoting Bone Health in Layer Chickens from the Perspective of Mitochondrial Energy Metabolism in Osteoclasts.Animals : an open access journal from MDPI · 2026Review
- Multivariate genetic analysis reveals three distinct pathological dimensions in musculoskeletal disorders.Nature communications · 2026Article
- TFE3 fusion proteins driveFrontiers in immunology · 2026Article
- PGC-1α: key regulator of mitochondrial biogenesis and cellular differentiation in metabolic and regenerative tissues.Cell & bioscience · 2025Review
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- Metabolic Rewiring and Post-Translational Modifications: Unlocking the Mechanisms of Bone Turnover in Osteoporosis.Aging and disease · 2025Review
- PRMT6 Epigenetically Drives Metabolic Switch from Fatty Acid Oxidation toward Glycolysis and Promotes Osteoclast Differentiation During Osteoporosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- L-arginine metabolism inhibits arthritis and inflammatory bone loss.Annals of the rheumatic diseases · 2024Article
- Role and Regulation of Transcription Factors in Osteoclastogenesis.International journal of molecular sciences · 2023Review
- Emerging roles of TFE3 in metabolic regulation.Cell death discovery · 2023Review
- Determination of the physiological range of oxygen tension in bone marrow monocytes using two-photon phosphorescence lifetime imaging microscopy.Scientific reports · 2022Article
- Application of metabolomics in osteoporosis research.Frontiers in endocrinology · 2022Review
- Osteoclasts adapt to physioxia perturbation through DNA demethylation.EMBO reports · 2021Article
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- Isovaleric acid ameliorates ovariectomy-induced osteoporosis by inhibiting osteoclast differentiation.Journal of cellular and molecular medicine · 2021Article
- Folliculin: A Regulator of Transcription Through AMPK and mTOR Signaling Pathways.Frontiers in cell and developmental biology · 2021Review
- Characterisation of genetic regulatory effects for osteoporosis risk variants in human osteoclasts.Genome biology · 2020Article
- FLCN alteration drives metabolic reprogramming towards nucleotide synthesis and cyst formation in salivary gland.Biochemical and biophysical research communications · 2020Article
Corrections and comments
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Authors and funding
21 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoclast differentiation is a dynamic differentiation process, which is accompanied by dramatic changes in metabolic status as well as in gene expression. Recent findings have revealed an essential connection between metabolic reprogramming and dynamic gene expression changes during osteoclast differentiation. However, the upstream regulatory mechanisms that drive these metabolic changes in osteoclastogenesis remain to be elucidated. Here, we demonstrate that induced deletion of a tumor suppressor gene, Folliculin (Flcn), in mouse osteoclast precursors causes severe osteoporosis in 3 weeks through excess osteoclastogenesis. Flcn-deficient osteoclast precursors reveal cell autonomous accelerated osteoclastogenesis with increased sensitivity to receptor activator of NF-κB ligand (RANKL). We demonstrate that Flcn regulates oxidative phosphorylation and purine metabolism through suppression of nuclear localization of the transcription factor Tfe3, thereby inhibiting expression of its target gene Pgc1. Metabolome studies revealed that Flcn-deficient osteoclast precursors exhibit significant augmentation of oxidative phosphorylation and nucleotide production, resulting in an enhanced purinergic signaling loop that is composed of controlled ATP release and autocrine/paracrine purinergic receptor stimulation. Inhibition of this purinergic signaling loop efficiently blocks accelerated osteoclastogenesis in Flcn-deficient osteoclast precursors. Here, we demonstrate an essential and novel role of the Flcn-Tfe3-Pgc1 axis in osteoclastogenesis through the metabolic reprogramming of oxidative phosphorylation and purine metabolism. © 2018 The Authors Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).
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