Evidence map›Paper›PMID 25532480›Full record

ArticleBone2015

Prevention of glucocorticoid induced-apoptosis of osteoblasts and osteocytes by protecting against endoplasmic reticulum (ER) stress in vitro and in vivo in female mice.

Amy Y Sato, Xiaolin Tu, Kevin A McAndrews, Lilian I Plotkin, Teresita Bellido

Open access · greenAbstract readComparative Study
In one paragraph

Article in Bone, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed
5.5field-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

85 citing papers in PubMed, 141 citations in OpenAlex.

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25 more citing papers are in PubMed but not listed here.

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

5 authors at 2 institutions in 1 country.

Amy Y SatoDepartment of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Xiaolin TuDepartment of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Kevin A McAndrewsDepartment of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA; Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA.
Lilian I PlotkinDepartment of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA; Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA.
Teresita BellidoDepartment of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Medicine, Division of Endocrinology, Indiana University School of Medicine, Indianapolis, IN, USA; Roudebush Veterans Administration Medical Center, Indianapolis, IN, USA. Electronic address: tbellido@iupui.edu.
Richard L. Roudebush VA Medical Center · USIndiana University School of Medicine

Funding

Glucocorticoid-induced Atrophy in Bone and MuscleR01AR059357 · NIAMS · UNIV OF ARKANSAS FOR MED SCIS · PI BELLIDO, TERESITA M. · 2011 to 2022
$3.4M
Osteocyte control of bone formation via SostR01DK076007 · NIDDK · UNIV OF ARKANSAS FOR MED SCIS · PI BELLIDO, TERESITA M. · 2007 to 2010
$1.4M
SkyScan 1172 High-resolution desk-top micro-CT systemS10RR023710 · NCRR · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI WILLIAMS, JAMES C · 2007 to 2007
$297k
PTH receptor Signaling and Diabetes-induced Bone DiseaseI01BX002104 · VA · RLR VA MEDICAL CENTER · PI BELLIDO, TERESITA M. · 2014 to 2023
–
BLRD VA I01 BX002104BLRD VA IK6 BX004596NCRR NIH HHS S10 RR023710NIAMS NIH HHS R01 AR059357NIDDK NIH HHS R01 DK076007
6 · The paper itself

Abstract

Endoplasmic reticulum (ER) stress is associated with increased reactive oxygen species (ROS), results from accumulation of misfolded/unfolded proteins, and can trigger apoptosis. ER stress is alleviated by phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), which inhibits protein translation allowing the ER to recover, thus promoting cell viability. We investigated whether osteoblastic cell apoptosis induced by glucocorticoids (GCs) is due to induction of ROS/ER stress and whether inhibition of eIF2α dephosphorylation promotes survival opposing the deleterious effects of GC in vitro and in vivo. Apoptosis of osteocytic MLO-Y4 and osteoblastic OB-6 cells induced by dexamethasone was abolished by ROS inhibitors. Like GC, the ER stress inducing agents brefeldin A and tunicamycin induced osteoblastic cell apoptosis. Salubrinal or guanabenz, specific inhibitors of eIF2α dephosphorylation, blocked apoptosis induced by either GC or ER stress inducers. Moreover, GC markedly decreased mineralization in OB-6 cells or primary osteoblasts; and salubrinal or guanabenz increased mineralization and prevented the inhibitory effect of GC. Furthermore, salubrinal (1 mg/kg/day) abolished osteoblast and osteocyte apoptosis in cancellous and cortical bone and partially prevented the loss of BMD at all sites and the decreased vertebral cancellous bone formation induced by treatment with prednisolone for 28 days (1.4 mg/kg/day). We conclude that part of the pro-apoptotic actions of GC on osteoblastic cells is mediated through ER stress, and that inhibition of eIF2α dephosphorylation protects from GC-induced apoptosis of osteoblasts and osteocytes in vitro and in vivo and from the deleterious effects of GC on the skeleton.

Indexed as

AnimalsApoptosisEndoplasmic ReticulumFemaleGlucocorticoidsIn Vitro TechniquesMiceOsteoblastsOsteocytesPhosphorylationGlucocorticoidsEndoplasmic reticulum stressGlucocorticoid-induced osteoporosisOsteoblastsOsteocytes

Identifiers

PMID25532480
PMCPMC4336847
OpenAlexW2080121305

What OpenQuestion holds

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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.