Evidence map›Paper›PMID 28801211›Full record

ArticleOsteoarthritis and cartilage2018

Parkin clearance of dysfunctional mitochondria regulates ROS levels and increases survival of human chondrocytes.

M Y Ansari, N M Khan, I Ahmad, T M Haqqi

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Osteoarthritis and cartilage, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
134citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

134 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Targeting the SARM1-cADPR-CaArthritis research & therapy · 2026
    Article
  6. Review
  7. Review
  8. Article
  9. Programmed cell death in osteoarthritis.Apoptosis : an international journal on programmed cell death · 2026
    Review
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Review
  17. Article
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  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

M Y AnsariDepartment of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
N M KhanDepartment of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
I AhmadDepartment of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
T M HaqqiDepartment of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, OH 44272, USA. Electronic address: thaqqi@neomed.edu.

Funding

Uridylation of miRNAs by ZCCHC6 Regulates IL-6 Expression in ArthritisR01AR067056 · NIAMS · NORTHEAST OHIO MEDICAL UNIVERSITY · PI HAQQI, TARIQ M · 2015 to 2019
$2.9M
Suppression of SHH Expression in Arthritis by Butea monospermaR01AT007373 · NCCIH · NORTHEAST OHIO MEDICAL UNIVERSITY · PI HAQQI, TARIQ M · 2013 to 2017
$2.5M
Suppression of MMP-13 Expression in Arthritis by PomegranateR01AT005520 · NCCIH · NORTHEAST OHIO MEDICAL UNIVERSITY · PI HAQQI, TARIQ M · 2010 to 2014
$1.9M
NCCIH NIH HHS R01 AT005520NCCIH NIH HHS R01 AT007373NIAMS NIH HHS R01 AR067056
6 · The paper itself

Abstract

objectiveMitochondrial dysfunction, oxidative stress and chondrocyte death are important contributors to the development and pathogenesis of osteoarthritis (OA). In this study, we determined the expression and role of Parkin in the clearance of damaged/dysfunctional mitochondria, regulation of reactive oxygen species (ROS) levels and chondrocyte survival under pathological conditions.

methodsHuman chondrocytes were from the unaffected area of knee OA cartilage (n = 12) and were stimulated with IL-1β to mimic pathological conditions. Mitochondrial membrane depolarization and ROS levels were determined using specific dyes and flow cytometry. Autophagy was determined by Western blotting for ATG5, Beclin1, immunofluorescence staining and confocal microscopy. Gene expression was determined by RT-qPCR. siRNA, wild-type and mutant Parkin plasmids were transfected using Amaxa system. Apoptosis was determined by PI staining of chondrocytes and TUNEL assay.

resultsIL-1β-stimulated OA chondrocytes showed high levels of ROS generation, mitochondrial membrane damage, accumulation of damaged mitochondria and higher incidence of apoptosis. IL-1β stimulation of chondrocytes with depleted Parkin expression resulted in sustained high levels of ROS, accumulation of damaged/dysfunctional mitochondria and enhanced apoptosis. Parkin translocation to depolarized/damaged mitochondria and recruitment of p62/SQSTM1 was required for the elimination of damaged/dysfunctional mitochondria in IL-1β-stimulated OA chondrocytes. Importantly we demonstrate that Parkin elimination of depolarized/damaged mitochondria required the Parkin ubiquitin ligase activity and resulted in reduced ROS levels and inhibition of apoptosis in OA chondrocytes under pathological conditions.

conclusionsOur data demonstrates that Parkin functions to eliminate depolarized/damaged mitochondria in chondrocytes which is necessary for mitochondrial quality control, regulation of ROS levels and chondrocyte survival under pathological conditions.

Indexed as

ApoptosisBlotting, WesternCells, CulturedCell SurvivalChondrocytesHumansMembrane Potential, MitochondrialMitochondriaOsteoarthritis, KneePolymerase Chain ReactionReactive Oxygen SpeciesUbiquitin-Protein Ligasesparkin proteinReactive Oxygen SpeciesUbiquitin-Protein LigasesChondrocytesMitochondrial dysfunctionOsteoarthritisParkinROS

Identifiers

PMID28801211
PMCPMC5803469

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Registered trials

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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.