Evidence map›Paper›PMID 27568565›Full record

ArticleCell reports2016

NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone.

Ryan E Tomlinson, Zhi Li, Qian Zhang, Brian C Goh, Zhu Li, Daniel L J Thorek, Labchan Rajbhandari, Thomas M Brushart, Liliana Minichiello, Fengquan Zhou and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers.

0numbers the graph read from it
0cells of the map it votes in
134citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

134 citing papers in PubMed, 206 citations in OpenAlex.

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  14. [Bifunctional biomaterials: An innovative strategy for synergistic bone tumor therapy and bone regeneration].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026
    Review
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  19. Neural Orchestration of Mandibular Development.International dental journal · 2026
    Review
  20. Article

74 more citing papers are in PubMed but not listed here.

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

12 authors at 3 institutions in 2 countries.

Ryan E TomlinsonDepartment of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD 21287, USA.
Zhi LiDepartment of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD 21287, USA.
Qian ZhangDepartment of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD 21287, USA.
Brian C GohDepartment of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD 21287, USA.
Zhu LiDepartment of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD 21287, USA.
Daniel L J ThorekDepartment of Radiology and Radiological Sciences, Johns Hopkins University, Baltimore, MD 21287, USA; Department of Oncology, Johns Hopkins University, Baltimore, MD 21287, USA.
Labchan RajbhandariDepartment of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
Thomas M BrushartDepartment of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD 21287, USA.
Liliana MinichielloDepartment of Pharmacology, Oxford University, Oxford OX1 3QT, UK.
Fengquan ZhouDepartment of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD 21287, USA.
Arun VenkatesanDepartment of Neurology, Johns Hopkins University, Baltimore, MD 21287, USA.
Thomas L ClemensDepartment of Orthopaedic Surgery, Johns Hopkins University, Baltimore, MD 21287, USA; Baltimore Veterans Administration Medical Center, Baltimore, MD 21201, USA. Electronic address: tclemen5@jhmi.edu.
Johns Hopkins University · USUnited States Department of Veterans Affairs · USUniversity of Oxford · GB

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007309 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI COX, ANDREA L · 1985 to 2019
$43.2M
Neuronal Regulation of Skeletal Development and RepairR01AR068934 · NIAMS · JOHNS HOPKINS UNIVERSITY · PI CLEMENS, THOMAS L · 2015 to 2019
$1.8M
Epigenetic regulation of neuronal morphogenesis in development and regenerationR01NS085176 · NINDS · JOHNS HOPKINS UNIVERSITY · PI ZHOU, FENGQUAN · 2014 to 2018
$1.8M
NIAMS NIH HHS R01 AR068934NIGMS NIH HHS T32 GM007309NINDS NIH HHS R01 NS085176
6 · The paper itself

Abstract

Developing tissues dictate the amount and type of innervation they require by secreting neurotrophins, which promote neuronal survival by activating distinct tyrosine kinase receptors. Here, we show that nerve growth factor (NGF) signaling through neurotrophic tyrosine kinase receptor type 1 (TrkA) directs innervation of the developing mouse femur to promote vascularization and osteoprogenitor lineage progression. At the start of primary ossification, TrkA-positive axons were observed at perichondrial bone surfaces, coincident with NGF expression in cells adjacent to centers of incipient ossification. Inactivation of TrkA signaling during embryogenesis in TrkA(F592A) mice impaired innervation, delayed vascular invasion of the primary and secondary ossification centers, decreased numbers of Osx-expressing osteoprogenitors, and decreased femoral length and volume. These same phenotypic abnormalities were observed in mice following tamoxifen-induced disruption of NGF in Col2-expressing perichondrial osteochondral progenitors. We conclude that NGF serves as a skeletal neurotrophin to promote sensory innervation of developing long bones, a process critical for normal primary and secondary ossification.

Indexed as

Neovascularization, PhysiologicOsteogenesisSignal TransductionAnimalsAnimals, NewbornEmbryo, MammalianFemurHindlimbMiceNerve Growth FactorReceptor, trkASensory Receptor CellsNerve Growth FactorReceptor, trkAendochondral bonenerve growth factorneurotrophic tyrosine kinase receptor type 1sensory nerves

Identifiers

PMID27568565
PMCPMC5014649
OpenAlexW2509759882

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.