ArticleEBioMedicine2020
The neuropeptide calcitonin gene-related peptide alpha is essential for bone healing.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Unravelling novel and pleiotropic genes for cannon bone circumference and bone mineral density in Yorkshire pigs.Journal of animal science · 2024Pooled it
- Reprogramming bone homeostasis: The recoupling-oriented framework of bidirectional regulation strategies for osteoporosis.iScience · 2026Review
- Sensing the skeleton: sensorineural regulation in bone.Nature reviews. Neuroscience · 2026Review
- 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
- Elevated fracture risk in a Danish cohort with type 2 diabetes mellitus and microvascular diseases.JBMR plus · 2026Article
- Neuroimmune Regulation in Posttraumatic Bone Repair: From Inflammatory Transition to Neurovascular Coupling and Functional Recovery.Journal of cellular physiology · 2026Review
- 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
- Neurogenic heterotopic ossification: from molecular mechanisms to clinical treatment.Journal of orthopaedic translation · 2026Review
- From force to resorption: mechanotransduction, osteoclasts, prevention.Progress in orthodontics · 2026Review
- Neural regulation of bone: from central neural circuits to peripheral innervation of the skeletal stem cell niche.Bone research · 2026Review
- Sensory Nerve-Derived CGRP Controls Osteoclastogenesis by Limiting Macrophage Bioenergetics in Bone Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Composite hydrogel-microsphere delivery system promotes early nerve-mediated bone regeneration and late-stage mechanotransduction-driven bone remodeling via sequential release of NGF and Yoda1.Bioactive materials · 2026Article
- CGRP Enhances the Regeneration of Bone Defects by Regulating Bone Marrow Mesenchymal Stem Cells Through Promoting ANGPTL4 Secretion by Bone Blood Vessels.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The calcitonin receptor controls osteophyte formation, but not cartilage degeneration and subchondral bone loss in experimental osteoarthritis.Bone & joint research · 2026Article
- Biomaterial-assisted neuralization strategies for tissue engineering applications.Materials today. Bio · 2026Review
- Neuro-immune-bone axis in post-traumatic bone regeneration: temporal regulation, dysregulation mechanisms, and therapeutic implications.Frontiers in immunology · 2026Review
- Engineering a functional tendon-bone interface: mechanisms and prospects of magnesium alloys in promoting neurotized regeneration via modulating stem cell-nerve interplay.Frontiers in medicine · 2026Review
- Sensory-neuron-derived CGRPα controls white adipocyte differentiation and tissue plasticity.Cell reports · 2025Article
- Nociceptive sensory neuron-derived NGF orchestrates a fibrotic mesenchymal stromal cell neurogenic niche to drive tendon pathological fibrosis.Nature communications · 2025Article
- Reduced somatosensory innervation alters the skeletal transcriptome at a single cell level in a mouse model of type 2 diabetes.Bone research · 2025Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImpaired fracture healing represents an ongoing clinical challenge, as treatment options remain limited. Calcitonin gene-related peptide (CGRP), a neuropeptide targeted by emerging anti-migraine drugs, is also expressed in sensory nerve fibres innervating bone tissue.
methodBone healing following a femoral osteotomy stabilized with an external fixator was analysed over 21 days in αCGRP-deficient and WT mice. Bone regeneration was evaluated by serum analysis, µCT analysis, histomorphometry and genome-wide expression analysis. Bone-marrow-derived osteoblasts and osteoclasts, as well as the CGRP antagonist olcegepant were employed for mechanistic studies.
findingsWT mice with a femoral fracture display increased CGRP serum levels. αCGRP mRNA expression after skeletal injury is exclusively induced in callus tissue, but not in other organs. On protein level, CGRP and its receptor, calcitonin receptor-like receptor (CRLR) complexing with RAMP1, are differentially expressed in the callus during bone regeneration. On the other hand, αCGRP-deficient mice display profoundly impaired bone regeneration characterised by a striking reduction in the number of bone-forming osteoblasts and a high rate of incomplete callus bridging and non-union. As assessed by genome-wide expression analysis, CGRP induces the expression of specific genes linked to ossification, bone remodeling and adipogenesis. This suggests that CGRP receptor-dependent PPARγ signaling plays a central role in fracture healing.
interpretationThis study demonstrates an essential role of αCGRP in orchestrating callus formation and identifies CGRP receptor agonism as a potential approach to stimulate bone regeneration. Moreover, as novel agents blocking CGRP or its receptor CRLR are currently introduced clinically for the treatment of migraine disorders, their potential negative impact on bone regeneration warrants clinical investigation.
fundingThis work was funded by grants from the Else-Kröner-Fresenius-Stiftung (EKFS), the Deutsche Forschungsgemeinschaft (DFG), and the Berlin Institute of Health (BIH).
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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.