Cytoskeletal dissolution blocks oxidant release and cell death in injured cartilage
Open Access
- 16 September 2011
- journal article
- research article
- Published by Wiley in Journal of Orthopaedic Research
- Vol. 30 (4), 593-598
- https://doi.org/10.1002/jor.21552
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/cm2) 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. © 2011 Orthopaedic Research Society. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:593–598, 2012This publication has 33 references indexed in Scilit:
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