Evidence map›Paper›PMID 22540193›Full record

ArticleBMC biology2012

BMP2 and mechanical loading cooperatively regulate immediate early signalling events in the BMP pathway.

Jessica Kopf, Ansgar Petersen, Georg N Duda, Petra Knaus

Open access · goldAbstract read
In one paragraph

Article in BMC biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

60 citing papers in PubMed, 117 citations in OpenAlex.

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  8. Mechanobiology in medicine · 2024
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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

4 authors at 3 institutions in 1 country.

Jessica KopfInstitute for Chemistry/Biochemistry, FU Berlin, Berlin, Germany.
Ansgar Petersen
Georg N Duda
Petra Knaus
Freie Universität Berlin · DEBerlin-Brandenburger Centrum für Regenerative Therapien · DECharité - Universitätsmedizin Berlin · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEfficient osteogenic differentiation is highly dependent on coordinated signals arising from growth factor signalling and mechanical forces. Bone morphogenetic proteins (BMPs) are secreted proteins that trigger Smad and non-Smad pathways and thereby influence transcriptional and non-transcriptional differentiation cues. Crosstalk at multiple levels allows for promotion or attenuation of signalling intensity and specificity. Similar to BMPs, mechanical stimulation enhances bone formation. However, the molecular mechanism by which mechanical forces crosstalk to biochemical signals is still unclear.

resultsHere, we use a three-dimensional bioreactor system to describe how mechanical forces are integrated into the BMP pathway. Time-dependent phosphorylation of Smad, mitogen-activated protein kinases and Akt in human fetal osteoblasts was investigated under loading and/or BMP2 stimulation conditions. The phosphorylation of R-Smads is increased both in intensity and duration under BMP2 stimulation with concurrent mechanical loading. Interestingly, the synergistic effect of both stimuli on immediate early Smad phosphorylation is reflected in the transcription of only a subset of BMP target genes, while others are differently affected. Together this results in a cooperative regulation of osteogenesis that is guided by both signalling pathways.

conclusionsMechanical signals are integrated into the BMP signalling pathway by enhancing immediate early steps within the Smad pathway, independent of autocrine ligand secretion. This suggests a direct crosstalk of both mechanotransduction and BMP signalling, most likely at the level of the cell surface receptors. Furthermore, the crosstalk of both pathways over longer time periods might occur on several signalling levels.

Indexed as

Mechanotransduction, CellularOsteogenesisSignal TransductionBioreactorsBlotting, WesternBone Morphogenetic Protein 2FetusHumansMitogen-Activated Protein KinasesOsteoblastsPhosphorylationPolymerase Chain ReactionProto-Oncogene Proteins c-aktReceptor Cross-TalkSmad5 ProteinBone Morphogenetic Protein 2Mitogen-Activated Protein KinasesProto-Oncogene Proteins c-aktSmad5 Protein

Identifiers

PMID22540193
PMCPMC3361481
OpenAlexW2159639395

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.