Evidence map›Paper›PMID 32299362›Full record

ArticleBMC molecular and cell biology2020

EphB4/ TNFR2/ERK/MAPK signaling pathway comprises a signaling axis to mediate the positive effect of TNF-α on osteogenic differentiation.

Yu Zhang, Chengzhe Yang, Shaohua Ge, Limei Wang, Jin Zhang, Pishan Yang

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

Article in BMC molecular and cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 31% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 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

6 authors at 1 institution in 1 country.

Yu ZhangShandong Provincial Key Laboratory of Oral Tissue Regeneration, Department of Endodontics, School of Stomatology, Shandong University, No. 44-1 Wenhua Road West, Jinan, Shandong Province, China.
Chengzhe YangDepartment of Oral & Maxillofacial Surgery, Qilu Hospital, Institute of Stomatology, Shandong University, No. 107 Wenhua Road West, Jinan, Shandong Province, China.
Shaohua GeShandong Provincial Key Laboratory of Oral Tissue Regeneration, Department of Endodontics, School of Stomatology, Shandong University, No. 44-1 Wenhua Road West, Jinan, Shandong Province, China.
Limei WangDepartment of Oral Medicine, Qilu Hospital, Institute of Stomatology, Shandong University, No. 107 Wenhua Road West, Jinan, Shandong Province, China.
Jin ZhangShandong Provincial Key Laboratory of Oral Tissue Regeneration, Department of Endodontics, School of Stomatology, Shandong University, No. 44-1 Wenhua Road West, Jinan, Shandong Province, China. teadenzj@sdu.edu.cn.
Pishan YangShandong Provincial Key Laboratory of Oral Tissue Regeneration, Department of Endodontics, School of Stomatology, Shandong University, No. 44-1 Wenhua Road West, Jinan, Shandong Province, China. yangps@sdu.edu.cn.
Shandong University · CN

Funding

National Natural Science Foundation of China 81702684National Natural Science Foundation of China 81771076
6 · The paper itself

Abstract

backgroundLow concentrations of tumor necrosis factor-alpha (TNF-α) and its receptor TNFR2 are both reported to promote osteogenic differentiation of osteoblast precursor cells. Moreover, low concentrations of TNF-α up-regulate the expression of EphB4. However, the molecular mechanisms underlying TNF-α-induced osteogenic differentiation and the roles of TNFR2 and EphB4 have not been fully elucidated.

resultsThe ALP activity, as well as the mRNA and protein levels of RUNX2, BSP, EphB4 and TNFR2, was significantly elevated in MC3T3-E1 murine osteoblast precursor cells when stimulated with 0.5 ng/ml TNF-α. After TNFR2 was inhibited by gene knockdown with lentivirus-mediated shRNA interference or by a neutralizing antibody against TNFR2, the pro-osteogenic effect of TNF-α was partly reversed, while the up-regulation of EphB4 by TNF-α remained unchanged. With EphB4 forward signaling suppressed by a potent inhibitor of EphB4 auto-phosphorylation, NVP-BHG712, TNF-α-enhanced expressions of TNFR2, BSP and Runx2 were significantly decreased. Further investigation into the signaling pathways revealed that TNF-α significantly increased levels of p-JNK, p-ERK and p-p38. However, only the p-ERK level was significantly inhibited in TNFR2-knockdown cells. In addition, the ERK pathway inhibitor, U0126 (10 μM), significantly reversed the positive effect of TNF-α on the protein levels of RUNX2 and BSP.

conclusionsThe EphB4, TNFR2 and ERK/MAPK signaling pathway comprises a signaling axis to mediate the positive effect of TNF-α on osteogenic differentiation.

Indexed as

Alkaline PhosphataseAnimalsButadienesCell LineCore Binding Factor Alpha 1 SubunitExtracellular Signal-Regulated MAP KinasesGene Knockdown TechniquesIntegrin-Binding SialoproteinMAP Kinase Kinase 4MAP Kinase Signaling SystemMiceNitrilesOsteoblastsOsteogenesisp38 Mitogen-Activated Protein KinasesPhosphorylationAlkaline PhosphataseButadienesCore Binding Factor Alpha 1 SubunitEphb4 protein, mouseExtracellular Signal-Regulated MAP KinasesIbsp protein, mouseIntegrin-Binding SialoproteinMAP Kinase Kinase 4NitrilesNVP-BHG712p38 Mitogen-Activated Protein KinasesPyrazolesPyrimidinesReceptor, EphB4Receptors, Tumor Necrosis Factor, Type IIRNA, Small InterferingRunx2 protein, mouseTumor Necrosis Factor-alphaU 0126EphB4MAPK cascadesOsteogenesisTNF-αTumor necrosis factor receptor2 (TNFR2)

Identifiers

PMID32299362
PMCPMC7164363
OpenAlexW3016990504

What OpenQuestion 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 OpenQuestion graph.