ArticleThe Journal of clinical investigation2020
Muscle-derived interleukin 6 increases exercise capacity by signaling in osteoblasts.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.
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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
88 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.
- Characteristics of the Protocols Used in Electrical Pulse Stimulation of Cultured Cells for Mimicking In Vivo Exercise: A Systematic Review, Meta-Analysis, and Meta-Regression.International journal of molecular sciences · 2022Pooled it
- Exercise Training Reduces the Inflammatory Response and Promotes Intestinal Mucosa-Associated Immunity in Lynch Syndrome.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Trial
- Biomaterials at the interface of bone-derived factors and inter-organ communication: Current evidence and future perspectives.Bioactive materials · 2026Review
- Exerkine-Mediated Inter-Organ Crosstalk and Translational Perspectives in Metabolic Diseases.Current obesity reports · 2026Review
- Muscle-Tumor Crosstalk in Exercise Oncology: Exercise-Induced Myokines and Cancer Cachexia.Cancers · 2026Review
- Mechanosensitive Piezo1/Osteocalcin/Irisin Axis Protects Against Disuse-Induced Muscle Atrophy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Exercise-induced myokines in metabolic regulation: mechanisms, mimetics, and translational potential.Archives of pharmacal research · 2026Review
- Bariatric Surgery and Metabolic Bone Disease: Crosstalk between Muscle, Adipose Tissue, and Bone.Obesity surgery · 2026Review
- [Liver-bone axis: novel mechanisms and strategies for MAFLD regulation].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- LDL receptor affects the skeletal muscle and bone microstructure of female mouse through the Wnt/β-catenin signaling pathway.Journal of molecular histology · 2026Article
- Stress-induced IL-6 regulation in pediatric bone growth disorders: current insights and therapeutic strategies.Frontiers in endocrinology · 2026Review
- Pectoral muscle cross-sectional area correlates with bone mineral density in postmenopausal women.Frontiers in medicine · 2026Article
- Exercise-responsive crosstalk within local muscle-bone units in osteosarcopenia: from mechanotransduction to secretome signalling.Frontiers in physiology · 2026Review
- Myokine Levels in Relation to Bone Markers and Adipokines in Children with Prader-Willi Syndrome During Growth Hormone Therapy and Dietary Intervention.International journal of molecular sciences · 2025Article
- Physical Activity, Exerkines, and Their Role in Cancer Cachexia.International journal of molecular sciences · 2025Review
- Exercise suppresses osteoclastogenesis by increasing the secretion of muscle-derived L-β-aminoisobutyric acid.Journal of sport and health science · 2025Article
- Exercise-Mediated Skeletal Muscle-Derived IL-6 Regulates Bone Metabolism: A New Perspective on Muscle-Bone Crosstalk.Biomolecules · 2025Review
- Bone-muscle interactions.Osteoporosis and sarcopenia · 2025Review
- Bone and muscle crosstalk in ageing and disease.Nature reviews. Endocrinology · 2025Review
- Role of Masticatory Force in Modulating Jawbone Immunity and Bone Homeostasis: A Review.International journal of molecular sciences · 2025Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 6 countries.
Funding
Abstract
Given the numerous health benefits of exercise, understanding how exercise capacity is regulated is a question of paramount importance. Circulating interleukin 6 (IL-6) levels surge during exercise and IL-6 favors exercise capacity. However, neither the cellular origin of circulating IL-6 during exercise nor the means by which this cytokine enhances exercise capacity has been formally established yet. Here we show through genetic means that the majority of circulating IL-6 detectable during exercise originates from muscle and that to increase exercise capacity, IL-6 must signal in osteoblasts to favor osteoclast differentiation and the release of bioactive osteocalcin in the general circulation. This explains why mice lacking the IL-6 receptor only in osteoblasts exhibit a deficit in exercise capacity of similar severity to the one seen in mice lacking muscle-derived IL-6 (mIL-6), and why this deficit is correctable by osteocalcin but not by IL-6. Furthermore, in agreement with the notion that IL-6 acts through osteocalcin, we demonstrate that mIL-6 promotes nutrient uptake and catabolism into myofibers during exercise in an osteocalcin-dependent manner. Finally, we show that the crosstalk between osteocalcin and IL-6 is conserved between rodents and humans. This study provides evidence that a muscle-bone-muscle endocrine axis is necessary to increase muscle function during exercise in rodents and humans.
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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.