Evidence map›Paper›PMID 33161099›Full record

ArticleOsteoarthritis and cartilage2021

Lysosomal dysfunction in osteoarthritis and aged cartilage triggers apoptosis in chondrocytes through BAX mediated release of Cytochrome c.

M Y Ansari, H C Ball, S J Wase, K Novak, T M Haqqi

Open access · greenAbstract read
In one paragraph

Article in Osteoarthritis and cartilage, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
6.5field-weighted citation impact, top 2% 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

45 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
  2. Review
  3. [Protective effect and mechanism of TSPAN9-mediated mitocytosis in interleukin-1β-induced rat chondrocyte senescence].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2026
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  15. Non-pathogenic Trojan horseMaterials today. Bio · 2024
    Article
  16. Article
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  18. Bats as instructive animal models for studying longevity and aging.Annals of the New York Academy of Sciences · 2024
    Review
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  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

5 authors at 1 institution in 1 country.

M Y AnsariDepartment of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
H C BallDepartment of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
S J WaseDepartment of Anatomy and Neurobiology, Northeast Ohio Medical University, Rootstown, OH 44272, USA.
K NovakDepartment 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.
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
Suppression of SHH Expression in Arthritis by Butea monospermaR01AT007373 · NCCIH · NORTHEAST OHIO MEDICAL UNIVERSITY · PI HAQQI, TARIQ M · 2013 to 2017
$2.5M
NCCIH NIH HHS R01 AT007373NIAMS NIH HHS R01 AR067056
6 · The paper itself

Abstract

objectiveLysosomes are the major catabolic organelle of the cell and regulate the macromolecular and organelle turnover and programmed cell death. Here, we investigated the lysosome dysfunction in cartilage and its role in chondrocytes apoptosis and the associated mechanism.

designLysosomal acidification in Osteoarthritis (OA) and aged cartilage was determined by LysoSensor staining. Lysosomal function in chondrocytes was blocked by siRNA mediated depletion of Lysosomal Associated Membrane Protein 2 (LAMP2) or with lysosome inhibitors. Chondrocyte apoptosis was determined by LDH release, Caspase-3/7 activation, TUNEL and PI uptake assays. Loss of mitochondrial membrane potential (MMP/ΔΨM) and mitochondrial superoxide level was determined by JC-1 and MitoSOX staining, respectively. Colocalization of mitochondria with BCL2 associated X (BAX) and Cytochrome c was determined by immunostaining. Destabilization of medial meniscus (DMM) was performed to induce OA in mice.

resultsLysosomal acidification was found to be significantly decreased in aged mouse and human and mouse OA cartilage which also showed increased chondrocyte apoptosis. Inhibition of lysosomal function resulted in increased oxidative stress, accumulation of dysfunctional mitochondria and apoptosis in chondrocytes in monolayer and in cartilage explant cultures. Depletion of LAMP2 expression or treatment of chondrocytes with lysosomal function inhibitors increased the expression and mitochondrial translocation of BAX leading to Cytochrome c release. Lysosomal dysfunction-induced apoptosis in chondrocytes was not blocked by antioxidants MitoTempo or Diphenyleneiodonium (DPI) but was abrogated by inhibiting BAX.

conclusionLysosomal dysfunction induce apoptosis in chondrocytes through BAX-mediated mitochondrial damage and release of Cytochrome c. Our data points to lysosomal function restoration and/or BAX inhibition in chondrocytes as a therapeutic approach for OA.

Indexed as

ApoptosisMembrane Potential, MitochondrialAgingAnimalsArthritis, Experimentalbcl-2-Associated X ProteinCartilage, ArticularChondrocytesCytochromes cHumansLysosomal-Associated Membrane Protein 2LysosomesMenisci, TibialMiceMitochondriaOsteoarthritis, Kneebcl-2-Associated X ProteinCytochromes cLysosomal-Associated Membrane Protein 2SuperoxidesAgeingLAMP1LAMP2LysosomesMitochondrial dysfunctionRedox

Identifiers

PMID33161099
PMCPMC8418332
OpenAlexW3017337165

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.