Evidence map›Paper›PMID 24853417›Full record

ArticleCell death & disease2014

IRE1a constitutes a negative feedback loop with BMP2 and acts as a novel mediator in modulating osteogenic differentiation.

F-J Guo, R Jiang, Z Xiong, F Xia, M Li, L Chen, C-J Liu

RetractedErratum issuedOpen access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.2field-weighted citation impact, top 23% 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

21 citing papers in PubMed, 31 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

F-J GuoDepartment of Cell Biology and Genetics, Core Facility of Development Biology, Chongqing Medical University, Chongqing, China.
R JiangLaboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing, China.
Z XiongDepartment of Cell Biology and Genetics, Core Facility of Development Biology, Chongqing Medical University, Chongqing, China.
F XiaDepartment of Cell Biology and Genetics, Core Facility of Development Biology, Chongqing Medical University, Chongqing, China.
M LiDepartment of Cell Biology and Genetics, Core Facility of Development Biology, Chongqing Medical University, Chongqing, China.
L ChenDepartment of Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
C-J LiuDepartments of Orthopaedic Surgery and Cell Biology, New York University School of Medicine, New York, NY, USA.
Chongqing Medical University · CNArmy Medical University · CNNew York University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bone morphogenetic protein 2 (BMP2) is known to activate unfolded protein response (UPR) signaling molecules, such as BiP (IgH chain-binding protein), PERK (PKR-like ER-resistant kinase), and IRE1α. Inositol-requiring enzyme-1a (IRE1a), as one of three unfolded protein sensors in UPR signaling pathways, can be activated during ER stress. Granulin-epithelin precursor (GEP) is an autocrine growth factor that has been implicated in embryonic development, tissue repair, tumorigenesis, and inflammation. However, the influence on IRE1a in BMP2-induced osteoblast differentiation has not yet been elucidated. Herein we demonstrate that overexpression of IRE1a inhibits osteoblast differentiation, as revealed by reduced activity of alkaline phosphatase (ALP) and osteocalcin; however, knockdown of IRE1a via the RNAi approach stimulates osteoblastogenesis. Mechanistic studies revealed that the expression of IRE1a during osteoblast was a consequence of JunB transcription factor binding to several AP1 sequence (TGAG/CTCA) in the 5'-flanking regulatory region of the IRE1a gene, followed by transcription. In addition, GEP induces IRE1a expressions and this induction of IRE1a by GEP depends on JunB. Furthermore, IRE1a inhibition of GEP-induced osteoblastogenesis relies on JunB. Besides, GEP is required for IRE1a inhibition of BMP2-induced bone formation. Collectively, these findings demonstrate that IRE1a negatively regulates BMP2-induced osteoblast differentiation and this IRE1a inhibition effect depends on GEP growth factor. Thus, IRE1a, BMP2, GEP growth factor, and JunB transcription factor form a regulatory loop and act in concert in the course of osteoblastogenesis.

Indexed as

Cell DifferentiationOsteogenesisSignal Transduction5' Flanking RegionAlkaline PhosphataseAnimalsBinding SitesBone Morphogenetic Protein 2Cell LineEndoribonucleasesFeedback, PhysiologicalFemaleIntercellular Signaling Peptides and ProteinsMesenchymal Stem CellsMiceMice, Inbred C57BLAlkaline PhosphataseBmp2 protein, mouseBone Morphogenetic Protein 2EndoribonucleasesErn1 protein, mouseIntercellular Signaling Peptides and ProteinsJunB protein, mouseOsteocalcinProgranulinsProtein Serine-Threonine KinasesTranscription Factor AP-1Transcription Factors

Identifiers

PMID24853417
PMCPMC4047903
OpenAlexW2067577926

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.