Mechanical Stress and ATP Synthesis are coupled by Mitochondrial Oxidants in Articular Cartilage

Katherine J Wolff; Prem S Ramakrishnan; Marc J Brouillette; Brice Journot; Todd O Mckinley; J A Buckwalter; James A Martin

doi:10.1002/jor.22223

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Mechanical Stress and ATP Synthesis are coupled by Mitochondrial Oxidants in Articular Cartilage

Journal article

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Mechanical Stress and ATP Synthesis are coupled by Mitochondrial Oxidants in Articular Cartilage

Katherine J Wolff, Prem S Ramakrishnan, Marc J Brouillette, Brice Journot, Todd O Mckinley, J A Buckwalter and James A Martin

Journal of orthopaedic research, Vol.31(2), pp.191-196

02/2013

DOI: 10.1002/jor.22223

PMCID: PMC3678272

PMID: 22930474

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Abstract

Metabolic adaptation of articular cartilage under joint loading is evident and matrix synthesis seems to be critically tied to ATP. Chondrocytes utilize the glycolytic pathway for energy requirements but seem to require mitochondrial reactive oxygen species (ROS) to sustain ATP synthesis. The role of ROS in regulating ATP reserves under a mechanically active environment is not clear. It is believed that physiological strains cause deformation of the mitochondria, potentially releasing ROS for energy production. We hypothesized that mechanical loading stimulates ATP synthesis via mitochondrial release of ROS. Bovine osteochondral explants were dynamically loaded at 0.5Hz with amplitude of 0.25MPa for 1 Hour. Cartilage response to mechanical loading was assessed by imaging with dihydroethidium (ROS indicator) and a Luciferase based ATP assay. Electron transport inhibitor rotenone and mitochondrial ROS scavenger MitoQ significantly suppressed mechanically induced ROS production and ATP synthesis. Our findings indicate that mitochondrial ROS are produced as a result of physiological mechanical strains. Taken together with our previous findings of ROS involvement in blunt impact injuries, mitochondrial ROS are important contributors to cartilage metabolic adaptation and their precise role in the pathogenesis of osteoarthritis warrants further investigation.

Glycolysis

Reactive Oxygen Species

Oxidants

Mechanical stress

Articular Cartilage

Details

Title: Subtitle: Mechanical Stress and ATP Synthesis are coupled by Mitochondrial Oxidants in Articular Cartilage
Creators: Katherine J Wolff - Carver College of Medicine, University of Iowa
Prem S Ramakrishnan - Ignacio Ponsetti Orthopaedic Cell Biology Lab Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City
Marc J Brouillette - Biomedical Engineering, University of Iowa
Brice Journot - Biomedical Engineering, University of Iowa
Todd O Mckinley - Ignacio Ponsetti Orthopaedic Cell Biology Lab Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City
J A Buckwalter - Ignacio Ponsetti Orthopaedic Cell Biology Lab Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City
James A Martin - Ignacio Ponsetti Orthopaedic Cell Biology Lab Department of Orthopaedics and Rehabilitation, University of Iowa, Iowa City
Resource Type: Journal article
Publication Details: Journal of orthopaedic research, Vol.31(2), pp.191-196
DOI: 10.1002/jor.22223
PMID: 22930474
PMCID: PMC3678272
NLM abbreviation: J Orthop Res
ISSN: 0736-0266
eISSN: 1554-527X
Grant note: P50 AR055533 || AR / National Institute of Arthritis and Musculoskeletal and Skin Diseases : NIAMS
Language: English
Date published: 02/2013
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: 9984040227502771

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