ArticleThe Journal of clinical investigation2023
Glucose- and glutamine-dependent bioenergetics sensitize bone mechanoresponse after unloading by modulating osteocyte calcium dynamics.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
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- AKT1 phosphorylates PRMT7 to promote GLUD1 methylation and gastric cancer progression.Cell death & disease · 2026Article
- Advancements in bone organoids: perspectives on construction methodologies and application strategies.Journal of advanced research · 2026Review
- HIF-1α and BMAL1 in bone regeneration: crosstalk between hypoxia response and circadian rhythm.Bone research · 2026Review
- Polycaprolactone scaffolds promote a regeneration-supportive metabolic response attenuated in diabetes.Regenerative biomaterials · 2026Article
- The regulatory networks and mechanisms of bone microenvironment in tumorigenesis and metastasis.Journal of bone oncology · 2025Review
- Modifications to the gut microbiome alter bone matrix proteomics and fracture toughness at the cellular scale.bioRxiv : the preprint server for biology · 2025Article
- Integrating 3D Osteocyte Culture, Microgravity Simulation, and Fluid Flow Reveals Mechanisms of Osteocyte Mechanosensation and Calcium Signaling Altered by Disuse.Biomolecules · 2025Article
- Accelerated osteocytic citrate production in chronic kidney disease is associated with protection of the kidney.bioRxiv : the preprint server for biology · 2025Article
- Aging and Altered Gravity: A Cellular Perspective.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- Ropivacaine Mediates Mitochondrial Dysfunction and CaNeurochemical research · 2025Article
- KLF6-mediated glutamine metabolism governs odontogenic differentiation and matrix mineralization of dental pulp stem cells.Stem cell research & therapy · 2025Article
- Mechanistic insights into bone destruction in multiple myeloma: Cellular and molecular perspectives.Journal of bone oncology · 2025Review
- Toward a clear relationship between mechanical signals and bone adaptation.Mechanobiology in medicine · 2025Review
- HK2-mediated Glycolysis Inhibits Mineralization of Cementoblasts Under Compression by Suppressing the Piezo1/Wnt Signaling.International journal of medical sciences · 2025Article
- Enhanced osteogenic differentiation in 3D hydrogel scaffold via macrophage mitochondrial transfer.Journal of nanobiotechnology · 2024Article
- Tricarboxylic Acid Cycle Regulation of Metabolic Program, Redox System, and Epigenetic Remodeling for Bone Health and Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Glutamine suppresses senescence and promotes autophagy through glycolysis inhibition-mediated AMPKα lactylation in intervertebral disc degeneration.Communications biology · 2024Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Disuse osteoporosis is a metabolic bone disease resulting from skeletal unloading (e.g., during extended bed rest, limb immobilization, and spaceflight), and the slow and insufficient bone recovery during reambulation remains an unresolved medical challenge. Here, we demonstrated that loading-induced increase in bone architecture/strength was suppressed in skeletons previously exposed to unloading. This reduction in bone mechanosensitivity was directly associated with attenuated osteocytic Ca2+ oscillatory dynamics. The unloading-induced compromised osteocytic Ca2+ response to reloading resulted from the HIF-1α/PDK1 axis-mediated increase in glycolysis, and a subsequent reduction in ATP synthesis. HIF-1α also transcriptionally induced substantial glutaminase 2 expression and thereby glutamine addiction in osteocytes. Inhibition of glycolysis by blockade of PDK1 or glutamine supplementation restored the mechanosensitivity in those skeletons with previous unloading by fueling the tricarboxylic acid cycle and rescuing subsequent Ca2+ oscillations in osteocytes. Thus, we provide mechanistic insight into disuse-induced deterioration of bone mechanosensitivity and a promising therapeutic approach to accelerate bone recovery after long-duration disuse.
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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.