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Rotenone prevents impact‐induced chondrocyte death
Author(s) -
Goodwin Wendy,
McCabe Daniel,
Sauter Ellen,
Reese Eric,
Walter Morgan,
Buckwalter Joseph A.,
Martin James A.
Publication year - 2010
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.21091
Subject(s) - chondrocyte , superoxide , rotenone , chemistry , oxidative stress , apoptosis , reactive oxygen species , mitochondrion , osteoarthritis , programmed cell death , andrology , pharmacology , medicine , in vitro , biochemistry , pathology , alternative medicine , enzyme
Mechanical insult to articular cartilage kills chondrocytes, an event that may increase the risk of posttraumatic osteoarthritis. Recent reports indicate that antioxidants decrease impact‐induced chondrocyte death, but the source(s) of oxidants, the time course of oxidant release, and the identity of the oxidative species generated in response to injury are unknown. A better understanding of these processes could lead to new treatments of acute joint injuries. To that end, we studied the kinetics and distribution of oxidant production in osteochondral explants subjected to a single, blunt‐impact injury. We followed superoxide production by measuring the time‐dependent accumulation of chondrocyte nuclei stained with the superoxide‐sensitive probe dihydroethidium. The percentage of chondrocytes that were dihydroethidium‐positive was 35% above baseline 10 min after impact, and 65% above baseline 60 min after impact. Most positive cells were found within and near areas contacted directly by the impact platen. Rotenone, an electron transport chain inhibitor, was used to test the hypothesis that mitochondria contribute to superoxide release. Rotenone treatment significantly reduced dihydroethidium staining, which remained steady at 15% above baseline for up to 60 min postimpact. Moreover, rotenone reduced chondrocyte death in impact sites by more than 40%, even when administered 2 h after injury ( p < 0.001). These data show that much of the acute chondrocyte mortality caused by in vitro impact injuries results from superoxide release from mitochondria, and suggest that brief exposure to free radical scavengers could significantly improve chondrocyte viability following joint injury. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1057–1063, 2010