Evidence map›Paper›PMID 22982228›Full record

ArticleBiochimica et biophysica acta2012

Endoplasmic reticulum stress induces the expression of COX-2 through activation of eIF2α, p38-MAPK and NF-κB in advanced glycation end products stimulated human chondrocytes.

Zafar Rasheed, Tariq M Haqqi

Open access · greenAbstract readComparative Study
In one paragraph

Article in Biochimica et biophysica acta, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
3.5field-weighted citation impact, top 8% 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

47 citing papers in PubMed, 102 citations in OpenAlex.

  1. Review
  2. The IRE1Cell stress · 2026
    Article
  3. Article
  4. Article
  5. Observational
  6. Article
  7. Article
  8. Efficacy of Tounongsan decoction on pyogenic liver abscess: network pharmacology and clinical trial validation.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024
    Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Mechanisms underlying reduced weight gain in intestinal fatty acid-binding protein (IFABP) null mice.American journal of physiology. Gastrointestinal and liver physiology · 2020
    Article
  20. Article
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

2 authors at 1 institution in 1 country.

Zafar RasheedDepartment of Medicine, Division of Rheumatology, MetroHealth Medical Center, Cleveland, OH 44109, United States. zafarrasheed@rocketmail.com
Tariq M Haqqi
MetroHealth · US

Funding

Suppression of MMP-13 Expression in Arthritis by PomegranateR01AT005520 · NCCIH · NORTHEAST OHIO MEDICAL UNIVERSITY · PI HAQQI, TARIQ M · 2010 to 2014
$1.9M
MECHANISMS OF CHONDROPROTECTION BY POMEGRANATE FRUIT EXTRACTR01AT003627 · NCCIH · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI HAQQI, TARIQ M · 2007 to 2011
$1.7M
NCCIH NIH HHS R01-AT-003267NCCIH NIH HHS R01 AT003627NCCIH NIH HHS R01 AT005520NCCIH NIH HHS R01-AT-005520
6 · The paper itself

Abstract

introductionDuring aging, advanced glycation end products (AGEs) accumulate in articular cartilage. In this study we determined whether AGEs induce endoplasmic reticulum (ER) stress and studied the ER stress-activated pathways that stimulate cyclooxygenase-2 (COX-2) expression in human chondrocytes.

methodsChondrocytes were stimulated with AGE-BSA. Gene expression was determined by quantitative PCR and protein expression was studied by immunoblotting. Studies to elucidate involved pathways were executed using siRNAs and specific inhibitors of eukaryotic initiation factor-2α (eIF2α), MAPKs and NF-κB.

resultsAGE-BSA induced expression of GRP78 with concomitant increase in COX-2 expression was observed in human chondrocytes. In addition, expression of Bag-1, an ER stress marker was also increased by AGE-BSA. RAGE knockdown inhibited AGE-BSA-induced expression of GRP78 and COX-2. Treatment with eIF2α inhibitor or eIF2α knockdown inhibited AGE-BSA-induced expression of GRP78 and COX-2 with decreased PGE(2) production. Treatment with SB202190 inhibited AGE-BSA-induced expression of GRP78 and COX-2, while treatment with PD98051 inhibited AGE-BSA-induced GRP78 protein expression but had no effect on COX-2 protein expression. SP600125 had no effect on either GRP78 or COX-2 protein expression. Bay 11-7082 suppressed AGE-BSA-induced GRP78 and COX-2 expression. AGE-BSA-induced activation of NF-κB was inhibited by treatment with SB202190 and by eIF2α knockdown, but was not inhibited when chondrocytes were treated with SP600125 or PD98059.

conclusionThis study demonstrates that AGEs induce ER stress and stimulate the expression of COX-2 through eIF2α, p38-MAPK and NF-κB pathways in human chondrocytes. Our results provide important insights into cartilage degradation in osteoarthritis associated with latent ER stress.

Indexed as

AdultAgedBlotting, WesternCartilage, ArticularCell ProliferationChondrocytesCyclooxygenase 2Endoplasmic Reticulum Chaperone BiPEndoplasmic Reticulum StressEnzyme-Linked Immunosorbent AssayEukaryotic Initiation Factor-2FemaleGlycation End Products, AdvancedHumansMaleMiddle Agedadvanced glycation end products-bovine serum albuminCyclooxygenase 2Endoplasmic Reticulum Chaperone BiPEukaryotic Initiation Factor-2Glycation End Products, AdvancedHSPA5 protein, humanNF-kappa Bp38 Mitogen-Activated Protein KinasesPTGS2 protein, humanRNA, MessengerSerum Albumin, Bovine

Identifiers

PMID22982228
PMCPMC4509732
OpenAlexW1987254687

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.