Evidence map›Paper›PMID 31166033›Full record

ArticleJournal of orthopaedic research : official publication of the Orthopaedic Research Society2019

Suppression of Notch Signaling in Osteoclasts Improves Bone Regeneration and Healing.

Peeyush N Goel, Yasaman Moharrer, John H Hebb, Alexander J Egol, Gurpreet Kaur, Kurt D Hankenson, Jaimo Ahn, Jason W Ashley

Open access · bronzeAbstract read
In one paragraph

Article in Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

11 citing papers in PubMed, 23 citations in OpenAlex.

  1. Wound Healing and Angiogenic Profiling of Dermal Endothelial Cells Isolated From People With Type 2 Diabetes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
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  6. Review
  7. Article
  8. Review
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  10. Notch signalling pathway in development of cholangiocarcinoma.World journal of gastrointestinal oncology · 2020
    Review
  11. Review
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 5 institutions in 1 country.

Peeyush N GoelDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Yasaman MoharrerDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
John H HebbDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Alexander J EgolDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Gurpreet KaurDepartment of Biological Sciences, University of the Sciences, Philadelphia, Pennsylvania.
Kurt D HankensonDepartment of Orthopaedic Surgery, University of Michigan, Ann Arbor, Michigan.
Jaimo AhnDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Jason W AshleyDepartment of Biology, Eastern Washington University, Cheney, Washington.ORCID 0000-0003-1064-542X
Philadelphia VA Medical Center · USEastern Washington University · USGeorgetown University · USUniversity of Michigan · USUniversity of the Sciences · US

Funding

Overall: Resource-based Center for Musculoskeletal Disorders Research (Overall Application)P30AR069619 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI LOUIS J SOSLOWSKY · 2016 to 2026
$9.1M
AO Foundation S-16-12ANIAMS NIH HHS P30 AR069619NIAMS NIH HHS P30AR069619
6 · The paper itself

Abstract

Owing to the central role of osteoclasts in bone physiology and remodeling, manipulation of their maturation process provides a potential therapeutic strategy for treating bone diseases. To investigate this, we genetically inhibited the Notch signaling pathway in the myeloid lineage, which includes osteoclast precursors, using a dominant negative form of MAML (dnMAML) that inhibits the transcriptional complex required for downstream Notch signaling. Osteoclasts derived from dnMAML mice showed no significant differences in early osteoclastic gene expression compared to the wild type. Further, these demonstrated significantly lowered resorption activity using bone surfaces while retaining their osteoblast stimulating ability using ex vivo techniques. Using in vivo approaches, we detected significantly higher bone formation rates and osteoblast gene expression in dnMAML cohorts. Further, these mice exhibited increased bone/tissue mineral density compared to wild type and larger bony calluses in later stages of fracture healing. These observations suggest that therapeutic suppression of osteoclast Notch signaling could reduce, but not eliminate, osteoclastic resorption without suppression of restorative bone remodeling and, therefore, presents a balanced paradigm for increasing bone formation, regeneration, and healing. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2089-2103, 2019.

Indexed as

Bone RegenerationOsteogenesisSignal TransductionAnimalsBone RemodelingBone ResorptionBony CallusCell LineageFemaleFracture HealingGenotypeHeterozygoteMaleMiceMice, Inbred C57BLNuclear ProteinsMaml1 protein, mouseNuclear ProteinsReceptors, NotchTranscription Factorsbone formationfracture healingNotch signalingosteoblastsosteoclastsregeneration

Identifiers

PMID31166033
PMCPMC6739141
OpenAlexW2970694844

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.