Cytoskeletal dissolution blocks oxidant release and cell death in injured cartilage

Ellen Sauter; Joseph A Buckwalter; Todd O McKinley; James A Martin

doi:10.1002/jor.21552

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Cytoskeletal dissolution blocks oxidant release and cell death in injured cartilage

Journal article

Peer reviewed

Cytoskeletal dissolution blocks oxidant release and cell death in injured cartilage

Ellen Sauter, Joseph A Buckwalter, Todd O McKinley and James A Martin

Journal of orthopaedic research, Vol.30(4), pp.593-598

04/2012

DOI: 10.1002/jor.21552

PMCID: PMC3666162

PMID: 21928429

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Abstract

The mechanisms by which articular surface impact causes post-traumatic osteoarthritis are not well understood, but studies of cartilage explants implicate the mitochondrial electron transport chain as a source of oxidants that cause chondrocyte death from mechanical injury. The linkage of mitochondria to the cytoskeleton suggests that they might release oxidants in response to mechanical strain, an effect that disrupting the cytoskeleton would prevent. To test this we investigated the effects of agents that promote the dissolution of microfilaments (cytochalasin B) or microtubules (nocodazole) on oxidant production and chondrocyte death following impact injury. Osteochondral explants treated with cytochalasin B or nocodazole for 4 h were impacted (7 J/cm(2)) and stained for oxidant production directly after impact and for cell viability 24 h after impact. Surfaces within and outside impact sites were then imaged by confocal microscopy. Both agents significantly reduced impact-induced oxidant release (p < 0.05); however, cytochalasin B was more effective than nocodazole (>60% reduction vs. 40% reduction, respectively). Both agents also prevented impact induced cell death. Dissolution of the cytoskeleton by both drugs was confirmed by phalloidin staining and confocal microscopy. These findings show that chondrocyte mortality from impact injury depends substantially on mitochondrial-cytoskeletal linkage, suggesting new approaches to stem mechanically induced cartilage degeneration.

Chondrocytes - pathology

Cytochalasin B - pharmacology

Reactive Oxygen Species - metabolism

Menisci, Tibial - metabolism

Tubulin Modulators - pharmacology

Actins - metabolism

Nocodazole - pharmacology

Oxidants - metabolism

Mitochondria - metabolism

Chondrocytes - drug effects

Menisci, Tibial - pathology

Animals

Cell Death - physiology

Cattle

Cytoskeleton - metabolism

Tibial Meniscus Injuries

Chondrocytes - metabolism

Cytoskeleton - drug effects

Details

Title: Subtitle: Cytoskeletal dissolution blocks oxidant release and cell death in injured cartilage
Creators: Ellen Sauter - University of Iowa, Iowa City, Iowa 52242, USA
Joseph A Buckwalter
Todd O McKinley
James A Martin
Resource Type: Journal article
Publication Details: Journal of orthopaedic research, Vol.30(4), pp.593-598
DOI: 10.1002/jor.21552
PMID: 21928429
PMCID: PMC3666162
NLM abbreviation: J Orthop Res
ISSN: 0736-0266
eISSN: 1554-527X
Publisher: United States
Grant note: S10 RR025439 / NCRR NIH HHS P50 AR048939 / NIAMS NIH HHS P50 AR055533 / NIAMS NIH HHS
Language: English
Date published: 04/2012
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Injury Prevention Research Center
Record Identifier: 9984040291502771

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