Evidence mapPaperPMID 26844285Full record

ArticleEBioMedicine2015

Lansoprazole Upregulates Polyubiquitination of the TNF Receptor-Associated Factor 6 and Facilitates Runx2-mediated Osteoblastogenesis.

Kenichi Mishima, Hiroshi Kitoh, Bisei Ohkawara, Tatsuya Okuno, Mikako Ito, Akio Masuda, Naoki Ishiguro, Kinji Ohno

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

14 citing papers in PubMed, 24 citations in OpenAlex.

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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 1 institution in 1 country.

Kenichi MishimaDivision of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan; Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
Hiroshi KitohDepartment of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
Bisei OhkawaraDivision of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
Tatsuya OkunoDivision of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
Mikako ItoDivision of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
Akio MasudaDivision of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
Naoki IshiguroDepartment of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
Kinji OhnoDivision of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
Nagoya University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The transcription factor, runt-related transcription factor 2 (Runx2), plays a pivotal role in the differentiation of the mesenchymal stem cells to the osteochondroblast lineages. We found by the drug repositioning strategy that a proton pump inhibitor, lansoprazole, enhances nuclear accumulation of Runx2 and induces osteoblastogenesis of human mesenchymal stromal cells. Systemic administration of lansoprazole to a rat femoral fracture model increased osteoblastogenesis. Dissection of signaling pathways revealed that lansoprazole activates a noncanonical bone morphogenic protein (BMP)-transforming growth factor-beta (TGF-β) activated kinase-1 (TAK1)-p38 mitogen-activated protein kinase (MAPK) pathway. We found by in cellulo ubiquitination studies that lansoprazole enhances polyubiquitination of the TNF receptor-associated factor 6 (TRAF6) and by in vitro ubiquitination studies that the enhanced polyubiquitination of TRAF6 is attributed to the blocking of a deubiquitination enzyme, cylindromatosis (CYLD). Structural modeling and site-directed mutagenesis of CYLD demonstrated that lansoprazole tightly fits in a pocket of CYLD where the C-terminal tail of ubiquitin lies. Lansoprazole is a potential therapeutic agent for enhancing osteoblastic differentiation.

Indexed as

AnimalsBone Morphogenetic ProteinsCell DifferentiationCell LineCore Binding Factor Alpha 1 SubunitFracture HealingFractures, BoneHumansLansoprazoleMaleMAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesMiceModels, MolecularMolecular ConformationOsteoblastsBone Morphogenetic ProteinsCore Binding Factor Alpha 1 SubunitLansoprazoleMAP Kinase Kinase Kinase 7MAP Kinase Kinase Kinasesp38 Mitogen-Activated Protein KinasesProton Pump InhibitorsTNF Receptor-Associated Factor 6UbiquitinsCYLDDrug repositioningLansoprazoleOsteoblastogenesisRunx2TRAF6

Identifiers

PMID26844285
PMCPMC4703748
OpenAlexW2221260019

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.