Evidence map›Paper›PMID 32141629›Full record

ArticleJournal of orthopaedic research : official publication of the Orthopaedic Research Society2020

Modulation of Notch1 signaling regulates bone fracture healing.

Sanja Novak, Emilie Roeder, Benjamin P Sinder, Douglas J Adams, Chris W Siebel, Danka Grcevic, Kurt D Hankenson, Brya G Matthews, Ivo Kalajzic

Open access · greenAbstract read
In one paragraph

Article in Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

31 citing papers in PubMed, 42 citations in OpenAlex.

  1. Review
  2. Myeloid-Specific Deletion ofBiomedicines · 2026
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  16. Article
  17. Inhibition of CGRP signaling impairs fracture healing in mice.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023
    Article
  18. Article
  19. Article
  20. PDGF inhibits BMP2-induced bone healing.NPJ Regenerative medicine · 2023
    Article
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

9 authors at 5 institutions in 3 countries.

Sanja NovakDepartment of Reconstructive Sciences, UConn Health, Farmington, Connecticut.ORCID 0000-0002-8042-932X
Emilie RoederDepartment of Reconstructive Sciences, UConn Health, Farmington, Connecticut.
Benjamin P SinderDepartment of Reconstructive Sciences, UConn Health, Farmington, Connecticut.
Douglas J AdamsDepartment of Orthopedic Surgery, UConn Health, Farmington, Connecticut.
Chris W SiebelDepartment of Discovery Oncology, Genentech, Inc., South San Francisco, California.
Danka GrcevicDepartment of Physiology and Immunology, University of Zagreb, Zagreb, Croatia.
Kurt D HankensonDepartment of Orthopaedic Surgery, University of Michigan Medical School, Ann Arbor, Michigan.
Brya G MatthewsDepartment of Reconstructive Sciences, UConn Health, Farmington, Connecticut.
Ivo KalajzicDepartment of Reconstructive Sciences, UConn Health, Farmington, Connecticut.ORCID 0000-0002-6752-3442
UConn Health · USUniversity of Auckland · NZUniversity of Colorado Anschutz Medical Campus · USUniversity of Michigan · USUniversity of Zagreb · HR

Funding

Notch Signaling and Bone Fracture HealingR01AR055607 · NIAMS · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI Kurt David Hankenson, IVO Kalajzic · 2011 to 2026
$6.3M
Regulators of Ischemic Fracture HealingR01AR066028 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HANKENSON, KURT DAVID · 2015 to 2020
$2.7M
Growth Factor Based on Enhancement of Bone RepairR01AR070813 · NIAMS · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI KALAJZIC, IVO · 2017 to 2021
$1.7M
Connecticut Innovations 14-SCA-UCHC-02Connecticut Innovations 16-RMB-UCHC-10NIAMS NIH HHS AR055607NIAMS NIH HHS AR066028NIAMS NIH HHS AR070813NIAMS NIH HHS R01 AR055607NIAMS NIH HHS R01 AR066028NIAMS NIH HHS R01 AR070813PRORP-CDMRP OR140396
6 · The paper itself

Abstract

Fracture healing involves interactions of different cell types, driven by various growth factors, and signaling cascades. Periosteal mesenchymal progenitor cells give rise to the majority of osteoblasts and chondrocytes in a fracture callus. Notch signaling has emerged as an important regulator of skeletal cell proliferation and differentiation. We investigated the effects of Notch signaling during the fracture healing process. Increased Notch signaling in osteochondroprogenitor cells driven by overexpression of Notch1 intracellular domain (NICD1) (αSMACreERT2 mice crossed with Rosa-NICD1) during fracture resulted in less cartilage, more mineralized callus tissue, and stronger and stiffer bones after 3 weeks. Periosteal cells overexpressing NICD1 showed increased proliferation and migration in vitro. In vivo data confirmed that increased Notch1 signaling caused expansion of alpha-smooth muscle actin (αSMA)-positive cells and their progeny including αSMA-derived osteoblasts in the callus without affecting osteoclast numbers. In contrast, anti-NRR1 antibody treatment to inhibit Notch1 signaling resulted in increased callus cartilage area, reduced callus bone mass, and reduced biomechanical strength. Our study shows a positive effect of induced Notch1 signaling on the fracture healing process, suggesting that stimulating the Notch pathway could be beneficial for fracture repair.

Indexed as

Fracture HealingAnimalsFemaleMaleMesenchymal Stem CellsMiceReceptor, Notch1Notch1 protein, mouseReceptor, Notch1alpha-smooth muscle actinbone fractureinducible CreNotch signalingosteoblast differentiationperiosteal progenitors

Identifiers

PMID32141629
PMCPMC7483882
OpenAlexW3010471384

What OpenQuestion holds

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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.