Evidence map›Paper›PMID 34767958›Full record

ArticleOsteoarthritis and cartilage2022

ERK1/2-mediated activation of DRP1 regulates mitochondrial dynamics and apoptosis in chondrocytes.

M Y Ansari, K Novak, T M Haqqi

Open access · greenAbstract read
In one paragraph

Article in Osteoarthritis and cartilage, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

68 citing papers in PubMed, 80 citations in OpenAlex.

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8 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

3 authors at 1 institution in 1 country.

M Y AnsariDepartment of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, 44272, OH, USA. Electronic address: mansari1@neomed.edu.
K NovakDepartment of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, 44272, OH, USA. Electronic address: knovak1@neomed.edu.
T M HaqqiDepartment of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, 44272, OH, USA. Electronic address: thaqqi@neomed.edu.
Northeast Ohio Medical University · US

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
Mechanism of ZCCHC6 Regulation of Mitochondrial Dysfunction In Alzheimer's DiseaseR56AG069116 · NIA · NORTHEAST OHIO MEDICAL UNIVERSITY · PI HAQQI, TARIQ M · 2021 to 2021
$751k
NIAMS NIH HHS R01 AR067056NIA NIH HHS R56 AG069116
6 · The paper itself

Abstract

objectiveTo determine the Dynamin-related protein 1 (DRP1) regulation of mitochondrial fission in chondrocytes under pathological conditions, an area which is underexplored in osteoarthritis pathogenesis.

designDRP1 protein expression was determined by immunohistochemistry (IHC) or immunofluorescence (IF) staining of cartilage sections. IL-1β-induced DRP1 mRNA expression in chondrocytes was quantified by qPCR and protein expression by immunoblotting. Mitochondrial fragmentation in chondrocytes was visualized by MitoTracker staining or IF staining of mitochondrial marker proteins or by transient expression of mitoDsRed. Mitochondrial reactive oxygen species (ROS) levels were determined by MitoSOX staining. Apoptosis was determined by lactate dehydrogenase (LDH) release assay, Caspase 3/7 activity assay, propidium iodide (PI), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and IF staining of cleaved caspase 3. Cytochrome c release was determined by confocal microscopy. Surgical destabilization of the medial meniscus (DMM) was used to induce osteoarthritis (OA) in mice.

resultsExpression of DRP1 and mitochondrial damage was high in human OA cartilage and in the joints of mice subjected to DMM surgery which also showed increased chondrocytes apoptosis. IL-1β-induced mitochondrial network fragmentation and chondrocyte apoptosis via modulation of DRP1 expression and activity and induce apoptosis via Bax-mediated release of Cytochrome c. Pharmacological inhibition of DRP1 activity by Mdivi-1 blocked IL-1β-induced mitochondrial damage and apoptosis in chondrocytes. Additionally, IL-1β-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) is crucial for DRP1 activation and induction of mitochondrial network fragmentation in chondrocytes as these were blocked by inhibiting ERK1/2 activation.

conclusionsThese findings demonstrate that ERK1/2 is a critical player in DRP1-mediated induction of mitochondrial fission and apoptosis in IL-1β-stimulated chondrocytes.

Indexed as

AgedAnimalsApoptosisChondrocytesDynaminsFemaleHumansMaleMAP Kinase Signaling SystemMiceMiddle AgedMitochondrial DynamicsDNM1L protein, humanDynaminsApoptosisCytochrome cDNM1LMitochondrial fissionMitochondrial network fragmentationOsteoarthritis

Identifiers

PMID34767958
PMCPMC8792336
OpenAlexW3211996611

What OpenQuestion holds

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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.