ArticleNature metabolism2023
SIRT2 regulates extracellular vesicle-mediated liver-bone communication.
Article in Nature metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.
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Who cites it
47 citing papers in PubMed, 2 syntheses or guidelines pooled it, 74 citations in OpenAlex.
- Advances in research on the relationship between mitochondrial dysfunction and osteoporosis: a bibliometric study from 2014 to 2024.Frontiers in medicine · 2025Pooled it
- Sirtuins in intervertebral disc degeneration: current understanding.Molecular medicine (Cambridge, Mass.) · 2024Pooled it
- Bioactive glasses-mediated ion therapy ameliorates hepatic osteodystrophy by reprogramming the liver-bone axis.Bioactive materials · 2027Article
- Multifunctional scaffold inspired by hepatocyte exosomes promotes bone regeneration by regulating osteogenic differentiation via PI3K/AKT pathway.Materials today. Bio · 2026Article
- The liver-bone axis: an emerging player in disease pathogenesis and therapeutic intervention.Science China. Life sciences · 2026Review
- The role and potential therapeutic intervention of cellular senescence in intervertebral disc degeneration.Genes & diseases · 2026Review
- Targeting adipocyte ESRRA alleviates osteoarthritis via interrupting inter-organelle crosstalk of complement C3-CFD-MAC cascade.Bone research · 2026Article
- Double-Pronged NAD Preservation: Delaying Cellular Senescence and Initiating Musculoskeletal Regeneration.Aging cell · 2026 · on this mapArticle
- RPS3-Enriched Extracellular Vesicles Mediate Liver-Spinal Cord Inter-Organ Communication.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Revealing the multiple faces of LRG1: gene expression, structure, function, and therapeutic potential.Journal of advanced research · 2026Review
- Hepatokine fibrinogen-like protein 1 drives liver-kidney crosstalk to promote renal fibrosis.Nature communications · 2026Article
- Non-Bone-Derived Extracellular Vesicles in Osteoporosis: Evidence Mapping and Nanomedicine Translation.International journal of nanomedicine · 2026Review
- OLINK proteomics identifies inflammatory protein signatures associated with vascular cognitive impairment in diabetes.Frontiers in immunology · 2026Article
- Liver-bone organoids reveal senescence-driven interorgan crosstalk.Bioactive materials · 2025Article
- Sirtuins as Therapeutic Targets for Treating Cancer, Metabolic Diseases, and Neurodegenerative Diseases.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The Role of Extracellular Vesicles in Musculoskeletal Diseases.Journal of extracellular vesicles · 2025Review
- The Mediating Role of Bioactive Molecules in Gut Microbiota-Bone Metabolism Crosstalk.Nutrients · 2025Review
- Exercise suppresses osteoclastogenesis by increasing the secretion of muscle-derived L-β-aminoisobutyric acid.Journal of sport and health science · 2025Article
- Discovery of novel SIRT2 inhibitors with anti-NSCLC activity through multi-virtual screening and biological evaluation.Future medicinal chemistry · 2025Article
- Toll-Like Receptors in the Immunotherapy Era: Dual-Edged Swords of Tumor Immunity and Clinical Translation.MedComm · 2025Review
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The interplay between liver and bone metabolism remains largely uncharacterized. Here, we uncover a mechanism of liver-bone crosstalk regulated by hepatocyte SIRT2. We demonstrate that hepatocyte SIRT2 expression is increased in aged mice and elderly humans. Liver-specific SIRT2 deficiency inhibits osteoclastogenesis and alleviates bone loss in mouse models of osteoporosis. We identify leucine-rich α-2-glycoprotein 1 (LRG1) as a functional cargo in hepatocyte-derived small extracellular vesicles (sEVs). In SIRT2-deficient hepatocytes, LRG1 levels in sEVs are upregulated, leading to increased transfer of LRG1 to bone-marrow-derived monocytes (BMDMs), and in turn, to inhibition of osteoclast differentiation via reduced nuclear translocation of NF-κB p65. Treatment with sEVs carrying high levels of LRG1 inhibits osteoclast differentiation in human BMDMs and in mice with osteoporosis, resulting in attenuated bone loss in mice. Furthermore, the plasma level of sEVs carrying LRG1 is positively correlated with bone mineral density in humans. Thus, drugs targeting hepatocyte-osteoclast communication may constitute a promising therapeutic strategy for primary osteoporosis.
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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.