Journal article
Rotenone prevents impact-induced chondrocyte death
Journal of orthopaedic research, Vol.28(8), pp.1057-1063
08/2010
DOI: 10.1002/jor.21091
PMCID: PMC3678274
PMID: 20108345
Abstract
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.
Details
- Title: Subtitle
- Rotenone prevents impact-induced chondrocyte death
- Creators
- Wendy Goodwin - Department of Orthopaedics and Rehabilitation, 1182 ML, The University of Iowa, 500 Newton Rd., Iowa City, Iowa 52242, USADaniel McCabeEllen SauterEric ReeseMorgan WalterJoseph A BuckwalterJames A Martin
- Resource Type
- Journal article
- Publication Details
- Journal of orthopaedic research, Vol.28(8), pp.1057-1063
- DOI
- 10.1002/jor.21091
- PMID
- 20108345
- PMCID
- PMC3678274
- NLM abbreviation
- J Orthop Res
- ISSN
- 0736-0266
- eISSN
- 1554-527X
- Publisher
- United States
- Grant note
- 1 P50 AR055533 / NIAMS NIH HHS P50 AR055533 / NIAMS NIH HHS
- Language
- English
- Date published
- 08/2010
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Stead Family Department of Pediatrics; Emergency Medicine; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Injury Prevention Research Center
- Record Identifier
- 9984040400002771
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