ArticleCommunications biology2018
mTORC1 impedes osteoclast differentiation via calcineurin and NFATc1.
Article in Communications biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
46 citing papers in PubMed, 63 citations in OpenAlex.
- Strontium-substituted hydroxyapatite nanoparticles as dual-function regulators of osteoblast mineralization and RANKL-induced osteoclastogenesis.Journal of materials science. Materials in medicine · 2026Article
- Therapeutic Efficacy of Sirolimus in Skeletal Manifestations of Gorham-Stout Disease in Adults: A Systematic Review.Cureus · 2026Review
- Design, synthesis and bioactivity of indobufen derivatives.RSC advances · 2026Article
- Human telomerase reverse transcriptase supports respiratory syncytial virus replication.Communications biology · 2026Article
- Branched‑chain amino acid metabolism and bone metabolism: Implications for osteoporosis pathogenesis and therapeutic strategies (Review).International journal of molecular medicine · 2026Review
- Mendelian Randomization Revealed Potential of mTOR Inhibitors for Treatment of Osteoporosis: Evidence From GWAS and Transcriptome Data.International journal of endocrinology · 2026Article
- Diverse effects of calcineurin in vascular smooth muscle cells: physiological activators and the controversial actions of clinical inhibitors.Frontiers in pharmacology · 2026Review
- mTOR Signaling in Macrophages: All Depends on the Context.International journal of molecular sciences · 2025Review
- RANKL blockade inhibits cancer growth through reversing the tolerogenic profile of tumor-infiltrating (plasmacytoid) dendritic cells.Journal for immunotherapy of cancer · 2025Article
- The novel organoselenium compound 4aa ameliorates osteoporosis by modulating gut microbiota composition and fecal metabolite profiles.Frontiers in endocrinology · 2025Article
- The mTOR pathway controls phosphorylation of BRAF at T401.Cell communication and signaling : CCS · 2024Article
- Osteoclasts control endochondral ossification via regulating acetyl-CoA availability.Bone research · 2024Article
- Article
- SHIP1 deficiency causes inflammation-dependent retardation in skeletal growth.Life science alliance · 2024Article
- Th17 Cells and IL-17A in Ischemic Stroke.Molecular neurobiology · 2024Review
- Restrained Mitf-associated autophagy by Mulberroside A ameliorates osteoclastogenesis and counteracts OVX-Induced osteoporosis in mice.Cell death discovery · 2024Article
- Rapamycin does not alter bone microarchitecture or material properties quality in young-adult and aged female C57BL/6 mice.JBMR plus · 2024Article
- Calcineurin Is a Universal Regulator of Vessel Function-Focus on Vascular Smooth Muscle Cells.Cells · 2023Review
- Tacrolimus Improves Therapeutic Efficacy of Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Diabetic Retinopathy by Suppressing DRP1-Mediated Mitochondrial Fission.Antioxidants (Basel, Switzerland) · 2023Article
- The role of NPY2R/NFATc1/DYRK1A regulatory axis in sebaceous glands for sebum synthesis.Cellular & molecular biology letters · 2023Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Rapamycins are immunosuppressant and anti-cancer drugs that inhibit the kinase mTOR. Clinically, they often cause bone pain, bone necrosis, and high bone turnover, yet the mechanisms are unclear. Here we show that mTORC1 activity is high in osteoclast precursors but downregulated upon RANKL treatment. Loss-of-function genetic models reveal that while early Raptor deletion in hematopoietic stem cells blunts osteoclastogenesis due to compromised proliferation/survival, late Raptor deletion in osteoclast precursors instead augments osteoclastogenesis. Gain-of-function genetic models by TSC1 deletion in HSCs or osteoclast precursors cause constitutive mTORC1 activation, impairing osteoclastogenesis. Pharmacologically, rapamycin treatment at low but clinically relevant doses exacerbates osteoclast differentiation and bone resorption, leading to bone loss. Mechanistically, RANKL inactivates mTORC1 via calcineurin-mediated mTORC1 dephosphorylation, consequently activating NFATc1 by reducing mTORC1-mediated NFATc1 phosphorylation. These findings uncover biphasic roles of mTORC1 in osteoclastogenesis, dosage-dependent effects of rapamycin on bone, and a previously unrecognized calcineurin-mTORC1-NFATc1 phosphorylation-regulatory signaling cascade.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.