Strain-Dependent Oxidant Release in Articular Cartilage Originates from Mitochondria

M J Brouillette; P S Ramakrishnan; V M Wagner; E E Sauter; B J Journot; T O McKinley; J A Martin

doi:10.1007/s10237-013-0518-8

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Strain-Dependent Oxidant Release in Articular Cartilage Originates from Mitochondria

Journal article

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Strain-Dependent Oxidant Release in Articular Cartilage Originates from Mitochondria

M J Brouillette, P S Ramakrishnan, V M Wagner, E E Sauter, B J Journot, T O McKinley and J A Martin

Biomechanics and modeling in mechanobiology, Vol.13(3), pp.565-572

06/2014

DOI: 10.1007/s10237-013-0518-8

PMCID: PMC3940668

PMID: 23896937

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Abstract

Mechanical loading is essential for articular cartilage homeostasis and plays a central role in the cartilage pathology, yet the mechanotransduction processes that underlie these effects remain unclear. Previously we showed that lethal amounts of reactive oxygen species (ROS) were liberated from the mitochondria in response to mechanical insult, and that chondrocyte deformation may be a source of ROS. To this end, we hypothesized that mechanically-induced mitochondrial ROS is related to the magnitude of cartilage deformation. To test this, we measured axial tissue strains in cartilage explants subjected to semi-confined compressive stresses of 0, 0.05, 0.1, 0.25, 0.5, or 1.0 MPa. The presence of ROS was then determined by confocal imaging with dihydroethidium (DHE), an oxidant sensitive fluorescent probe. Our results indicated that ROS levels increased linearly relative to the magnitude of axial strains (r 2 = 0.83, p < 0.05), and significant cell death was observed at strains > 40%. By contrast, hydrostatic stress, which causes minimal tissue strain, had no significant effect. Cell permeable superoxide dismutase mimetic Mn(III)tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTMPyP) significantly decreased ROS levels at 0.5 and 0.25 MPa. Electron transport chain inhibitor, rotenone, and cytoskeletal inhibitor, cytochalasin B, significantly decreased ROS levels at 0.25 MPa. Our findings strongly suggest that ROS and mitochondrial oxidants contribute to cartilage mechanobiology.

Cytoskeleton

Cartilage

Reactive Oxygen Species (ROS)

Chondrocyte

Static Stress

Superoxide

Hydrostatic Stress

Mechanical Loading

Details

Title: Subtitle: Strain-Dependent Oxidant Release in Articular Cartilage Originates from Mitochondria
Creators: M J Brouillette - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City
P S Ramakrishnan - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City
V M Wagner - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City
E E Sauter - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City
B J Journot - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City
T O McKinley - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City
J A Martin - Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City
Resource Type: Journal article
Publication Details: Biomechanics and modeling in mechanobiology, Vol.13(3), pp.565-572
DOI: 10.1007/s10237-013-0518-8
PMID: 23896937
PMCID: PMC3940668
NLM abbreviation: Biomech Model Mechanobiol
ISSN: 1617-7959
eISSN: 1617-7940
Language: English
Date published: 06/2014
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation
Record Identifier: 9984040261902771

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