Oxidant conditioning protects cartilage from mechanically induced damage

Prem Ramakrishnan; Benjamin A Hecht; Douglas R Pedersen; Matthew R Lavery; Jerry Maynard; Joseph A Buckwalter; James A Martin

doi:10.1002/jor.21072

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Oxidant conditioning protects cartilage from mechanically induced damage

Journal article

Open access

Peer reviewed

Oxidant conditioning protects cartilage from mechanically induced damage

Prem Ramakrishnan, Benjamin A Hecht, Douglas R Pedersen, Matthew R Lavery, Jerry Maynard, Joseph A Buckwalter and James A Martin

Journal of orthopaedic research, Vol.28(7), pp.914-920

07/2010

DOI: 10.1002/jor.21072

PMCID: PMC3708667

PMID: 20058262

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Abstract

Articular cartilage degeneration in osteoarthritis has been linked to abnormal mechanical stresses that are known to cause chondrocyte apoptosis and metabolic derangement in in vitro models. Evidence implicating oxidative damage as the immediate cause of these harmful effects suggests that the antioxidant defenses of chondrocytes might influence their tolerance for mechanical injury. Based on evidence that antioxidant defenses in many cell types are stimulated by moderate oxidant exposure, we hypothesized that oxidant preconditioning would reduce acute chondrocyte death and proteoglycan depletion in cartilage explants after exposure to abnormal mechanical stresses. Porcine cartilage explants were treated every 48 h with tert-butyl hydrogen peroxide (tBHP) at nonlethal concentrations (25, 100, 250, and 500 microM) for a varying number of times (one, two, or four) prior to a bout of unconfined axial compression (5 MPa, 1 Hz, 1800 cycles). When compared with untreated controls, tBHP had significant positive effects on post-compression viability, lactate production, and proteoglycan losses. Overall, the most effective regime was 100 microM tBHP applied four times. RNA analysis revealed significant effects of 100 microM tBHP on gene expression. Catalase, hypoxia-inducible factor-1alpha (HIF-1alpha), and glyceraldehyde 6-phosphate dehydrogenase (GAPDH) were significantly increased relative to untreated controls in explants treated four times with 100 microM tBHP, a regime that also resulted in a significant decrease in matrix metalloproteinase-3 (MMP-3) expression. These findings demonstrate that repeated exposure of cartilage to sublethal concentrations of peroxide can moderate the acute effects of mechanical stress, a conclusion supported by evidence of peroxide-induced changes in gene expression that could render chondrocytes more resistant to oxidative damage.

Oxidants - pharmacology

Gene Expression - drug effects

Apoptosis - drug effects

Oxidative Stress - physiology

Adaptation, Physiological - drug effects

Stress, Mechanical

Osteoarthritis - drug therapy

Osteoarthritis - physiopathology

Cartilage, Articular - physiopathology

Cartilage, Articular - metabolism

Gene Expression - physiology

tert-Butylhydroperoxide - pharmacology

Cell Survival - physiology

Compressive Strength - physiology

Cell Survival - drug effects

Catalase - genetics

Hypoxia-Inducible Factor 1, alpha Subunit - genetics

Lactic Acid - metabolism

Adaptation, Physiological - physiology

Osteoarthritis - metabolism

Glyceraldehyde-3-Phosphate Dehydrogenases - genetics

Aggrecans - genetics

Animals

Apoptosis - physiology

Matrix Metalloproteinase 3 - genetics

Sus scrofa

Details

Title: Subtitle: Oxidant conditioning protects cartilage from mechanically induced damage
Creators: Prem Ramakrishnan - Department of Orthopedics and Rehabilitation, The University of Iowa, 1182 ML, Iowa City, Iowa 52242, USA
Benjamin A Hecht
Douglas R Pedersen
Matthew R Lavery
Jerry Maynard
Joseph A Buckwalter
James A Martin
Resource Type: Journal article
Publication Details: Journal of orthopaedic research, Vol.28(7), pp.914-920
DOI: 10.1002/jor.21072
PMID: 20058262
PMCID: PMC3708667
NLM abbreviation: J Orthop Res
ISSN: 0736-0266
eISSN: 1554-527X
Publisher: United States
Grant note: P50 AR055533 / NIAMS NIH HHS
Language: English
Date published: 07/2010
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; Health, Sport, and Human Physiology
Record Identifier: 9984040273102771

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