ReviewArthritis research & therapy2014
The role of peripheral nerve fibers and their neurotransmitters in cartilage and bone physiology and pathophysiology.
Review in Arthritis research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 3 of them syntheses 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
125 citing papers in PubMed, 3 syntheses or guidelines pooled it, 214 citations in OpenAlex.
- Consequences of Aging on Bone.Aging and disease · 2023Pooled it
- Pooled it
- Neuroimmune expression in hip osteoarthritis: a systematic review.BMC musculoskeletal disorders · 2017Pooled it
- Calcitonin Gene-Related Peptide (CGRP) in Bone Repair and Musculoskeletal Pain: A Scoping Review of Skeletal Regeneration, Joint and Tendon Involvement, and CGRP-Targeted Therapies.Calcified tissue international · 2026Article
- Alzheimer's Disease Risk Factor APOE4 Exerts Dimorphic Effects on Female Bone.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Neural regulation of bone: from central neural circuits to peripheral innervation of the skeletal stem cell niche.Bone research · 2026Review
- Multifunctional ions/drugs co-delivering nanocomposite hydrogel orchestrates neuro-osteogenic microenvironment for boosting osteoporotic osseointegration.Journal of nanobiotechnology · 2026Article
- Mechanistic insights into cartilage-sensory nerve crosstalk in osteoarthritis progression.Journal of orthopaedic translation · 2026Review
- Osteoclast-Derived SLIT3 Mediates Osteoarthritis Pain and Degenerative Changes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Neural Orchestration of Mandibular Development.International dental journal · 2026Review
- A Biomimetic Norepinephrine-Loaded Aligned Mineralized Collagen Scaffold for Coordinated Neurovascular, Osteogenic, and Immunomodulatory Repair of Critical-Sized Bone Defects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Sympathetic regulation of bone homeostasis and remodeling: molecular mechanisms, pathophysiological roles, and therapeutic implications.Frontiers in immunology · 2026Review
- Exercise-Dependent effects of substance P deficiency on joint degeneration and inflammation in a surgical mouse model of osteoarthritis.Arthritis research & therapy · 2025Article
- Molecular mechanisms and therapeutic implications of the sympathetic nervous system in bone-related disorders: a brain-bone axis perspective.Bone research · 2025Review
- Sensory and Sympathetic Nerve Localization in Mouse Temporomandibular Joint and Knee Joint Neuro-Musculoskeletal Tissues.Orthodontics & craniofacial research · 2025Article
- A Multidimensional Definition of Pre-Osteoarthritis: Toward 21st-Century Subclinical Detection and Targeted Intervention.International journal of molecular sciences · 2025Review
- Association betweensubchondral bone sclerosis and pain in varus ankle osteoarthritis: a CT-based analysis using patient-reported outcomes.Archives of orthopaedic and trauma surgery · 2025Article
- Extracellular Vesicles Derived from Human Umbilical Cord-Mesenchymal Stem Cells Ameliorate Intervertebral Disc Degeneration.Biomedicines · 2025Article
- The Role of Oral and Gut Microbiota in Bone Health: Insights from Bacterial Extracellular Vesicles.Microorganisms · 2025Review
- Using ultrasound to define inflammatory and non-inflammatory phenotypes in difficult-to-treat psoriatic arthritis.RMD open · 2025Article
65 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
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The peripheral nervous system is critically involved in bone metabolism, osteogenesis, and bone remodeling. Nerve fibers of sympathetic and sensory origin innervate synovial tissue and subchondral bone of diathrodial joints. They modulate vascularization and matrix differentiation during endochondral ossification in embryonic limb development, indicating a distinct role in skeletal growth and limb regeneration processes. In pathophysiological situations, the innervation pattern of sympathetic and sensory nerve fibers is altered in adult joint tissues and bone. Various resident cell types of the musculoskeletal system express receptors for sensory and sympathetic neurotransmitters. Osteoblasts, osteoclasts, mesenchymal stem cells, synovial fibroblasts, and different types of chondrocytes produce distinct subtypes of adrenoceptors, receptors for vasointestinal peptide, for substance P and calcitonin gene-related peptide. Many of these cells even synthesize neuropeptides such as substance P and calcitonin gene-related peptide and are positive for tyrosine-hydroxylase, the rate-limiting enzyme for biosynthesis of catecholamines. Sensory and sympathetic neurotransmitters modulate osteo-chondrogenic differentiation of mesenchymal progenitor cells during endochondral ossification in limb development. In adults, sensory and sympathetic neurotransmitters are critical for bone regeneration after fracture and are involved in the pathology of inflammatory diseases as rheumatoid arthritis which manifests mainly in joints. Possibly, they might also play a role in pathogenesis of degenerative joint disorders, such as osteoarthritis. All together, accumulating data imply that sensory and sympathetic neurotransmitters have crucial trophic effects which are critical for proper limb formation during embryonic skeletal growth. In adults, they modulate bone regeneration, bone remodeling, and articular cartilage homeostasis in addition to their classic neurological actions.
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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.