ArticleCell stem cell2022
A cholinergic neuroskeletal interface promotes bone formation during postnatal growth and exercise.
Article in Cell stem cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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.
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Who cites it
36 citing papers in PubMed, 53 citations in OpenAlex.
- GFRα2 identified in TBI-induced bone healing is a novel therapeutic target for osteoporosis via osteogenesis and angiogenesis.Journal of orthopaedic translation · 2026Article
- Neuroendocrine and neural control of bone mass in health and disease.The Journal of clinical investigation · 2026Review
- Neural regulation of bone: from central neural circuits to peripheral innervation of the skeletal stem cell niche.Bone research · 2026Review
- The Neuro-Bone Axis in Metastatic Progression: Innervation, Neuro-Immune-Osteoclast Crosstalk, and Therapeutic Opportunities.Biology · 2026Review
- From nerve to bone: a tale of autonomic nervous system, bone cells, and beyond.Military Medical Research · 2026Review
- Sympathetic regulation of bone homeostasis and remodeling: molecular mechanisms, pathophysiological roles, and therapeutic implications.Frontiers in immunology · 2026Review
- Interorgan Communications in Skeletal Pathophysiology: From Molecular Pathways to Multidisciplinary Therapies.Research (Washington, D.C.) · 2026Review
- A single-cell hematopoietic microenvironmental atlas reveals progressive maturation of bone marrow vascular niche.Cell regeneration (London, England) · 2025Article
- Molecular mechanisms and therapeutic implications of the sympathetic nervous system in bone-related disorders: a brain-bone axis perspective.Bone research · 2025Review
- Mild photothermal-mediated neuroimmunomodulatory composite hydrogel ameliorates bone healing microenvironment for enhanced osteoporotic bone defect regeneration.Materials today. Bio · 2025Article
- New Insight into Bone Immunity in Marrow Cavity and Cancellous Bone Microenvironments and Their Regulation.Biomedicines · 2025Review
- Multi-omics Mendelian randomization integrating RNA-seq, eQTL and pQTL data revealed CPXM1 as a potential drug target for osteoporosis.Hereditas · 2025Article
- Cholinergic regulation of osteocyte mechanobiology: A paradigm for bone adaptation.Science advances · 2025Article
- Sympathetic cholinergic nerve fibres promote BMSC differentiation into osteoblasts via NRTN secretion: a potential treatment for osteoporosis.Journal of orthopaedic surgery and research · 2025Article
- Autonomic Nervous System in Bone Remodeling: From Mechanisms to Novel Therapies in Orthopedic Diseases.Orthopaedic surgery · 2025Review
- Targeting the central and peripheral nervous system to regulate bone homeostasis: mechanisms and potential therapies.Military Medical Research · 2025Review
- Strategies for promoting neurovascularization in bone regeneration.Military Medical Research · 2025Review
- A Novel Deer Antler-Inspired Bone Graft Triggers Rapid Bone Regeneration.Advanced materials (Deerfield Beach, Fla.) · 2025Article
- Deep imaging of LepRBone research · 2025Article
- Contemporary insights into neuroimmune interactions across development and aging.Frontiers in neurology · 2025Review
Corrections and comments
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Authors and funding
22 authors at 9 institutions in 5 countries.
Funding
Abstract
The autonomic nervous system is a master regulator of homeostatic processes and stress responses. Sympathetic noradrenergic nerve fibers decrease bone mass, but the role of cholinergic signaling in bone has remained largely unknown. Here, we describe that early postnatally, a subset of sympathetic nerve fibers undergoes an interleukin-6 (IL-6)-induced cholinergic switch upon contacting the bone. A neurotrophic dependency mediated through GDNF-family receptor-α2 (GFRα2) and its ligand, neurturin (NRTN), is established between sympathetic cholinergic fibers and bone-embedded osteocytes, which require cholinergic innervation for their survival and connectivity. Bone-lining osteoprogenitors amplify and propagate cholinergic signals in the bone marrow (BM). Moderate exercise augments trabecular bone partly through an IL-6-dependent expansion of sympathetic cholinergic nerve fibers. Consequently, loss of cholinergic skeletal innervation reduces osteocyte survival and function, causing osteopenia and impaired skeletal adaptation to moderate exercise. These results uncover a cholinergic neuro-osteocyte interface that regulates skeletogenesis and skeletal turnover through bone-anabolic effects.
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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.