Multiple signals induce endoplasmic reticulum stress in both primary and immortalized chondrocytes resulting in loss of differentiation, impaired cell growth, and apoptosis

Ling Yang; Sara G Carlson; Denise McBurney; Walter E Horton Jr

doi:10.1074/jbc.M501069200

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Multiple signals induce endoplasmic reticulum stress in both primary and immortalized chondrocytes resulting in loss of differentiation, impaired cell growth, and apoptosis

Journal article

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Multiple signals induce endoplasmic reticulum stress in both primary and immortalized chondrocytes resulting in loss of differentiation, impaired cell growth, and apoptosis

Ling Yang, Sara G Carlson, Denise McBurney and Walter E Horton Jr

The Journal of biological chemistry, Vol.280(35), pp.31156-31165

09/02/2005

DOI: 10.1074/jbc.M501069200

PMID: 16000304

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Abstract

The endoplasmic reticulum is the site of synthesis and folding of secretory proteins and is sensitive to changes in the internal and external environment of the cell. Both physiological and pathological conditions may perturb the function of the endoplasmic reticulum, resulting in endoplasmic reticulum stress. The chondrocyte is the only resident cell found in cartilage and is responsible for synthesis and turnover of the abundant extracellular matrix and may be sensitive to endoplasmic reticulum stress. Here we report that glucose withdrawal, tunicamycin, and thapsigargin induce up-regulation of GADD153 and caspase-12, two markers of endoplasmic reticulum stress, in both primary chondrocytes and a chondrocyte cell line. Other agents such as interleukin-1beta or tumor necrosis factor alpha induced a minimal or no induction of GADD153, respectively. The endoplasmic reticulum stress resulted in decreased chondrocyte growth based on cell counts, up-regulation of p21, and decreased PCNA expression. In addition, perturbation of endoplasmic reticulum function resulted in decreased accumulation of an Alcian Blue positive matrix by chondrocytes and decreased expression of type II collagen at the protein level. Further, quantitative real-time PCR was used to demonstrate a down-regulation of steady state mRNA levels coding for aggrecan, collagen II, and link protein in chondrocytes exposed to endoplasmic reticulum stress-inducing conditions. Ultimately, endoplasmic reticulum stress resulted in chondrocyte apoptosis, as evidenced by DNA fragmentation and annexin V staining. These findings have potentially important implications regarding consequences of endoplasmic reticulum stress in cartilage biology.

Biomarkers

Chondrocytes - cytology

Endoplasmic Reticulum - metabolism

Extracellular Matrix - metabolism

Collagen Type II - metabolism

Caspases - metabolism

Chondrocytes - physiology

Transcription Factor CHOP

DNA Fragmentation

Caspase 12

Cell Differentiation - physiology

Tunicamycin - metabolism

CCAAT-Enhancer-Binding Proteins - metabolism

Cells, Cultured

Gene Expression Regulation

Rats

Anti-Bacterial Agents - metabolism

Transcription Factors - metabolism

Annexin A5 - metabolism

Animals

Thapsigargin - metabolism

Glucose - metabolism

Signal Transduction - physiology

Apoptosis - physiology

Proliferating Cell Nuclear Antigen - metabolism

Details

Title: Subtitle: Multiple signals induce endoplasmic reticulum stress in both primary and immortalized chondrocytes resulting in loss of differentiation, impaired cell growth, and apoptosis
Creators: Ling Yang - Department of Anatomy, Northeastern Ohio University College of Medicine, Rootstown, Ohio 44272, USA
Sara G Carlson
Denise McBurney
Walter E Horton Jr
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.280(35), pp.31156-31165
DOI: 10.1074/jbc.M501069200
PMID: 16000304
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Language: English
Date published: 09/02/2005
Academic Unit: Molecular Physiology and Biophysics; Anatomy and Cell Biology
Record Identifier: 9984025334302771

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