ArticleScientific reports2023
Three-dimensional visualization of neural networks inside bone by Osteo-DISCO protocol and alteration of bone remodeling by surgical nerve ablation.
Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 14 citations in OpenAlex.
- Sensory nerves regulate bone homeostasis in response to mechanical unloading or reloading: evidence from a spaceflight experiment and ground-based mechanical unloading models.Bone research · 2026Article
- Three-dimensional visualization of nerves in bones of the human hand in osteoarthritis.JBMR plus · 2026Article
- 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
- Cellular and Molecular Neuro-Bone Cell Interactions Drive Alveolar Bone Remodeling During Orthodontic Mechanical Loading.International journal of biological sciences · 2026Review
- Peripheral neuronal sensitization and neurovascular remodelling in osteoarthritis pain.Nature reviews. Rheumatology · 2025Review
- KneEZ Clear, an Effective Tissue Clearing Protocol to Study Musculoskeletal Tissues in the Mouse.bioRxiv : the preprint server for biology · 2025Article
- Extensive Periosteal Injury During Fracture Induces Long-Term Pain in Mice.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2025Article
- Comprehensive 3D Imaging of Whole Zebrafish Using a Water-Based Clearing Reagent for Hard Tissues.Zebrafish · 2025Article
- Developing long bones respond to surrounding tissues by trans-pairing of periosteal osteoclasts and endocortical osteoblasts.Development (Cambridge, England) · 2024Article
- Role of the Neurologic System in Fracture Healing: An Extensive Review.Current osteoporosis reports · 2024Review
- Using tissue clearing and light sheet fluorescence microscopy for the three-dimensional analysis of sensory and sympathetic nerve endings that innervate bone and dental tissue of mice.The Journal of comparative neurology · 2024Article
- Role of the Peripheral Nervous System in Skeletal Development and Regeneration: Controversies and Clinical Implications.Current osteoporosis reports · 2023Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bone is one of the largest organ systems in humans and is considered to regulate whole-body homeostasis in cooperation with other organs. We have previously reported that a sympathetic or sensory nervous system inside bone regulates bone homeostasis. However, the detailed regulatory mechanism, including the distribution of nerves inside bone, remains unknown. Although a two-dimensional histological analysis has been widely used to evaluate the structure of nerves or blood vessels, the actual structure is more complex, suggesting that it should be evaluated three-dimensionally. Here, we established a novel bone tissue clearing technique (Osteo-DISCO) for murine bones which enabled us to visualize the detailed distribution of nerves or blood vessels inside bone. Interestingly, we found that there is a specific nerve entry site in each long bone and that surgical ablation of the specific nerve fibers entering bone tissue led to decreased bone formation and impaired bone regeneration. Furthermore, we revealed that the administration of calcitonin gene-related peptide (CGRP), which is primarily released from sensory nerves, suppressed the bone loss caused by surgical nerve ablation. An in vitro study also indicated that CGRP directly promotes osteoblast activity, suggesting that sensory nerves inside bone can regulate osteogenesis via the secretion of CGRP.
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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.