ArticleThe Journal of comparative neurology2024
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.
Article in The Journal of comparative neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Sensing the skeleton: sensorineural regulation in bone.Nature reviews. Neuroscience · 2026Review
- 3D Light sheet microscopy reveals aging osteoarthritis-associated joint-innervated nerve remodeling in mouse knee joints.Osteoarthritis and cartilage · 2026Article
- 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
- Mutual amplification of sensory nerve outgrowth and tumor progression in myeloma.Haematologica · 2026Article
- Article
- β-Adrenergic Signaling Promotes Anti-Tumor Immunity in TP53-mutant Oral Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Three-dimensional visualization of nerves in bones of the human hand in osteoarthritis.JBMR plus · 2026Article
- Aging disrupts sympathetic innervation of the thymus.Cell reports · 2026Article
- The Neuro-Bone Axis in Metastatic Progression: Innervation, Neuro-Immune-Osteoclast Crosstalk, and Therapeutic Opportunities.Biology · 2026Review
- Neural Orchestration of Mandibular Development.International dental journal · 2026Review
- Lung retention, distribution and persistence of polymer particles in rats exposed via inhalation.Particle and fibre toxicology · 2026Article
- Biomimetic Nanoparticles for Bone Regeneration: Construction Strategies and Therapeutic Mechanisms.International journal of nanomedicine · 2026Review
- Tumor-nerve crosstalk: peripheral mechanisms mediating bone tumor progression and cancer-induced bone pain.Frontiers in oncology · 2026Review
- Current progress of labeling strategies in tissue clearing for large-scale biological visualization.Frontiers in cell and developmental biology · 2026Review
- Multiscale 3D Whole Joint Cellular and Molecular Mapping Reveals Disease-Specific Neurovascular Plasticity Underlying the Structure-Pain Relationship.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Fast-conducting mechanonociceptors uniquely engage reflexive and affective pain circuitry to drive protective responses.bioRxiv : the preprint server for biology · 2025Article
- Not Just Neurons: Pain Is Orchestrated in Partnership with Many Non-neuronal Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Article
- An in vivo electrophysiological preparation for mechanical, electrical and optical stimulation of sensory neurons that innervate murine bone.Animal models and experimental medicine · 2025Article
- BigReg: an efficient registration pipeline for high-resolution X-ray and light-sheet fluorescence microscopy.Journal of medical imaging (Bellingham, Wash.) · 2025Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Bone and dental tissues are richly innervated by sensory and sympathetic neurons. However, the characterization of the morphology, molecular phenotype, and distribution of nerves that innervate hard tissue has so far mostly been limited to thin histological sections. This approach does not adequately capture dispersed neuronal projections due to the loss of important structural information during three-dimensional (3D) reconstruction. In this study, we modified the immunolabeling-enabled imaging of solvent-cleared organs (iDISCO/iDISCO+) clearing protocol to image high-resolution neuronal structures in whole femurs and mandibles collected from perfused C57Bl/6 mice. Axons and their nerve terminal endings were immunolabeled with antibodies directed against protein gene product 9.5 (pan-neuronal marker), calcitonin gene-related peptide (peptidergic nociceptor marker), or tyrosine hydroxylase (sympathetic neuron marker). Volume imaging was performed using light sheet fluorescence microscopy. We report high-quality immunolabeling of the axons and nerve terminal endings for both sensory and sympathetic neurons that innervate the mouse femur and mandible. Importantly, we are able to follow their projections through full 3D volumes, highlight how extensive their distribution is, and show regional differences in innervation patterns for different parts of each bone (and surrounding tissues). Mapping the distribution of sensory and sympathetic axons, and their nerve terminal endings, in different bony compartments may be important in further elucidating their roles in health and disease.
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