Evidence map›Paper›PMID 33335129›Full record

ArticleScientific reports2020

Local injections of β-NGF accelerates endochondral fracture repair by promoting cartilage to bone conversion.

Kevin O Rivera, Fabrizio Russo, Ryan M Boileau, Ryan E Tomlinson, Theodore Miclau, Ralph S Marcucio, Tejal A Desai, Chelsea S Bahney

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.7field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 39 citations in OpenAlex.

  1. Review
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  9. p75Bone reports · 2025
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  19. Neuronal regulation of bone and tendon injury repair: a focused review.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Kevin O RiveraGraduate Program in Oral and Craniofacial Sciences, School of Dentistry, University of California, San Francisco (UCSF), San Francisco, CA, USA.
Fabrizio RussoDepartment of Orthopaedics and Trauma Surgery, Campus Bio-Medico University, Rome, Italy.
Ryan M BoileauThe Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Center for Reproductive Sciences, University of California, San Francisco (UCSF), San Francisco, CA, USA.
Ryan E TomlinsonDepartment of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, PA, USA.
Theodore MiclauDepartment of Orthopaedic Surgery, Orthopaedic Trauma Institute, University of California, San Francisco (UCSF), San Francisco, CA, USA.
Ralph S MarcucioGraduate Program in Oral and Craniofacial Sciences, School of Dentistry, University of California, San Francisco (UCSF), San Francisco, CA, USA.
Tejal A DesaiGraduate Program in Oral and Craniofacial Sciences, School of Dentistry, University of California, San Francisco (UCSF), San Francisco, CA, USA.
Chelsea S BahneyGraduate Program in Oral and Craniofacial Sciences, School of Dentistry, University of California, San Francisco (UCSF), San Francisco, CA, USA. cbahney@sprivail.org.
University of California, San Francisco · USThomas Jefferson University · USUniversità Campus Bio-Medico · IT

Funding

Maximizing Opportunities for Research Excellence - Evaluation Training SupplementR25GM056847 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DUNCAN, D'ANNE S., SELLO, JASON K · 1998 to 2023
$14.1M
Skeletal Biology and Biomechanics (SBB) CoreP30AR075055 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Wenhan Chang · 2019 to 2026
$7.1M
UCSF Core Center for Musculoskeletal Biology and MedicineP30AR066262 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LOTZ, JEFFREY C. · 2014 to 2018
$3.0M
Neuronal Regulation of Skeletal Development and RepairR01AR068934 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI CLEMENS, THOMAS L · 2015 to 2019
$1.8M
NGF-TrkA Signaling in Dental Implant Osseointegration and OsseoperceptionR03DE028397 · NIDCR · THOMAS JEFFERSON UNIVERSITY · PI TOMLINSON, RYAN · 2019 to 2020
$312k
Local Delivery of Neurogenic Factors via Polymeric Microparticles for Enhanced Endochondral Bone Repair in the MandibleF31DE028485 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RIVERA, KEVIN OMAR · 2019 to 2020
$81k
NIAMS NIH HHS P30 AR066262NIAMS NIH HHS P30 AR075055NIAMS NIH HHS R01 AR068934NIAMS NIH HHS R01-AR068934NIDCR NIH HHS F31 DE028485NIDCR NIH HHS F31-DE028485NIDCR NIH HHS R03 DE028397NIGMS NIH HHS R25 GM056847NIGMS NIH HHS R25-GM056847
6 · The paper itself

Abstract

There are currently no pharmacological approaches in fracture healing designed to therapeutically stimulate endochondral ossification. In this study, we test nerve growth factor (NGF) as an understudied therapeutic for fracture repair. We first characterized endogenous expression of Ngf and its receptor tropomyosin receptor kinase A (TrkA) during tibial fracture repair, finding that they peak during the cartilaginous phase. We then tested two injection regimens and found that local β-NGF injections during the endochondral/cartilaginous phase promoted osteogenic marker expression. Gene expression data from β-NGF stimulated cartilage callus explants show a promotion in markers associated with endochondral ossification such as Ihh, Alpl, and Sdf-1. Gene ontology enrichment analysis revealed the promotion of genes associated with Wnt activation, PDGF- and integrin-binding. Subsequent histological analysis confirmed Wnt activation following local β-NGF injections. Finally, we demonstrate functional improvements to bone healing following local β-NGF injections which resulted in a decrease in cartilage and increase of bone volume. Moreover, the newly formed bone contained higher trabecular number, connective density, and bone mineral density. Collectively, we demonstrate β-NGF's ability to promote endochondral repair in a murine model and uncover mechanisms that will serve to further understand the molecular switches that occur during cartilage to bone transformation.

Indexed as

AnimalsBiomarkersCartilageDisease Models, AnimalFluorescent Antibody TechniqueFracture HealingGene Expression ProfilingImaging, Three-DimensionalImmunohistochemistryInjections, IntralesionalMiceNerve Growth FactorOsteogenesisRecombinant ProteinsTibial FracturesTime FactorsBiomarkersNerve Growth FactorRecombinant Proteins

Identifiers

PMID33335129
PMCPMC7747641
OpenAlexW3111887055

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.