Evidence map›Paper›PMID 22628200›Full record

ArticleJournal of cellular biochemistry2012

BMP2 induces osteoblast apoptosis in a maturation state and noggin-dependent manner.

Sharon L Hyzy, Rene Olivares-Navarrete, Zvi Schwartz, Barbara D Boyan

Open access · greenAbstract read
In one paragraph

Article in Journal of cellular biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

26 citing papers in PubMed, 47 citations in OpenAlex.

  1. Article
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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.

Sharon L HyzySchool of Biology, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Rene Olivares-Navarrete
Zvi Schwartz
Barbara D Boyan
Georgia Institute of Technology · USThe University of Texas Health Science Center at San Antonio · USThe Wallace H. Coulter Department of Biomedical Engineering · US

Funding

Mechanisms of Cell/Surface InteractionR01AR052102 · NIAMS · VIRGINIA COMMONWEALTH UNIVERSITY · PI BOYAN, BARBARA D. · 2006 to 2015
$3.3M
NIAMS NIH HHS AR052102NIAMS NIH HHS R01 AR052102
6 · The paper itself

Abstract

Large doses of bone morphogenetic protein 2 (BMP2) are used clinically to induce bone formation in challenging bone defects. However, complications after treatment include swelling, ectopic bone formation, and adjacent bone resorption. While BMP2 can be effective, it is important to characterize the mechanism of the deleterious effects to optimize its use. The aim of this study was to determine the effect of BMP2 on apoptosis in osteoblast lineage cells and to determine the role of the BMP inhibitor Noggin in this process. Human mesenchymal stem cells (MSCs), immature osteoblast-like MG63 cells, and mature normal human osteoblasts (NHOst) were treated with BMP2. A model system of increased endogenous BMP signaling was created by silencing Noggin (shNOG-MG63). Finally, the BMP pathway regulating apoptosis in NHOst was examined using BMP signaling inhibitors (5Z-7-oxozeaenol, dorsomorphin, H-8). Apoptosis was characterized by caspase-3, BAX/BCL2, p53, and DNA fragmentation. BMP2 induced apoptosis in a cell-type dependent manner. While the effect was minor in MSCs, MG63 cells had modest increases and NHOst cells had robust increases apoptosis after BMP2 treatment. Apoptosis was significantly higher in shNOG-MG63 than MG63 cells. 5Z-7-oxozeaenol and dorsomorphin eliminated the BMP2-induced increase in DNA fragmentation in NHOst, suggesting roles for TAB/TAK1 and Smad signaling. These results indicate that the apoptotic effect of BMP2 is dependent on cell maturation state, inducing apoptosis in committed osteoblasts through Smad and TAB/TAK1 signaling, and is regulated by Noggin. Dose and delivery must be optimized in therapeutic applications of BMP2 to minimize complications.

Indexed as

Apoptosisbcl-2-Associated X ProteinBone Morphogenetic Protein 2Bone Morphogenetic ProteinsCarrier ProteinsCaspase 3DNA FragmentationEnzyme ActivationHumansIn Situ Nick-End LabelingLactonesMesenchymal Stem CellsNoggin ProteinOsteoblastsPyrazolesPyrimidines7-oxozeanolBAX protein, humanbcl-2-Associated X ProteinBMP2 protein, humanBone Morphogenetic Protein 2Bone Morphogenetic ProteinsCarrier ProteinsCASP3 protein, humanCaspase 3dorsomorphinLactonesNoggin ProteinPyrazolesPyrimidinesRecombinant ProteinsResorcinolsRNA, MessengerZearalenone

Identifiers

PMID22628200
PMCPMC3852427
OpenAlexW2086739628

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.