Injurious Loading of Articular Cartilage Compromises Chondrocyte Respiratory Function

Mitchell C Coleman; Prem S Ramakrishnan; Marc J Brouillette; James A Martin

doi:10.1002/art.39460

Back

Injurious Loading of Articular Cartilage Compromises Chondrocyte Respiratory Function

Journal article

Open access

Injurious Loading of Articular Cartilage Compromises Chondrocyte Respiratory Function

Mitchell C Coleman, Prem S Ramakrishnan, Marc J Brouillette and James A Martin

Arthritis & rheumatology (Hoboken, N.J.), Vol.68(3), pp.662-671

03/2016

DOI: 10.1002/art.39460

PMCID: PMC4767543

PMID: 26473613

Files and links (1)

url

https://doi.org/10.1002/art.39460View

Published (Version of record) Open Access

Abstract

To determine whether repeatedly overloading healthy cartilage disrupts mitochondrial function in a manner similar to that associated with osteoarthritis (OA) pathogenesis. We exposed normal articular cartilage on bovine osteochondral explants to 1 day or 7 consecutive days of cyclic axial compression (0.25 MPa or 1.0 MPa at 0.5 Hz for 3 hours) and evaluated the effects on chondrocyte viability, ATP concentration, reactive oxygen species (ROS) production, indicators of oxidative stress, respiration, and mitochondrial membrane potential. Neither 0.25 MPa nor 1.0 MPa of cyclic compression caused extensive chondrocyte death, macroscopic tissue damage, or overt changes in stress-strain behavior. After 1 day of loading, differences in respiratory activities between the 0.25 MPa and 1.0 MPa groups were minimal; however, after 7 days of loading, respiratory activity and ATP levels were suppressed in the 1.0 MPa group relative to the 0.25 MPa group, an effect prevented by pretreatment with 10 mM N-acetylcysteine. These changes were accompanied by increased proton leakage and decreased mitochondrial membrane potential, as well as by increased ROS formation, as indicated by dihydroethidium staining and glutathione oxidation. Repeated overloading leads to chondrocyte oxidant-dependent mitochondrial dysfunction. This mitochondrial dysfunction may contribute to destabilization of cartilage during various stages of OA in distinct ways by disrupting chondrocyte anabolic responses to mechanical stimuli.

Reactive Oxygen Species - metabolism

Oxidation-Reduction

Glutathione - metabolism

Adenosine Triphosphate - analysis

Oxidative Stress - physiology

Cells, Cultured

Ethidium - metabolism

Glutathione Disulfide - metabolism

Animals

Cartilage, Articular - physiopathology

Chondrocytes - physiology

Cattle

Cell Respiration - physiology

Membrane Potential, Mitochondrial - physiology

In Vitro Techniques

Mitochondria - physiology

Ethidium - analogs & derivatives

Osteoarthritis - etiology

Cell Survival - physiology

Chondrocytes - metabolism

Details

Title: Subtitle: Injurious Loading of Articular Cartilage Compromises Chondrocyte Respiratory Function
Creators: Mitchell C Coleman - University of Iowa, Iowa City
Prem S Ramakrishnan - University of Iowa, Iowa City
Marc J Brouillette - University of Iowa, Iowa City
James A Martin - University of Iowa, Iowa City
Resource Type: Journal article
Publication Details: Arthritis & rheumatology (Hoboken, N.J.), Vol.68(3), pp.662-671
DOI: 10.1002/art.39460
PMID: 26473613
PMCID: PMC4767543
NLM abbreviation: Arthritis Rheumatol
ISSN: 2326-5191
eISSN: 2326-5205
Publisher: United States
Grant note: P50 AR055533 / NIAMS NIH HHS T32 CA078586 / NCI NIH HHS P30-CA-086862 / NCI NIH HHS P30 CA086862 / NCI NIH HHS
Language: English
Date published: 03/2016
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Orthopedics and Rehabilitation; Radiation Oncology
Record Identifier: 9984040224802771

Metrics

14 Record Views

77 Times Cited - Web of Science