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

Title

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

Creator

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

Publisher

The Journal of biological chemistry

Date

2005
2005-09

Description

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.

Subject

Animals; Annexin A5/metabolism; Anti-Bacterial Agents/metabolism; Apoptosis/*physiology; Biomarkers; Caspase 12; Caspases/metabolism; CCAAT-Enhancer-Binding Proteins/metabolism; Cell Differentiation/*physiology; Cells; Chondrocytes/cytology/*physiology; Collagen Type II/metabolism; Cultured; DNA Fragmentation; Endoplasmic Reticulum/*metabolism; Extracellular Matrix/metabolism; Gene Expression Regulation; Glucose/metabolism; Proliferating Cell Nuclear Antigen/metabolism; Rats; Signal Transduction/*physiology; Thapsigargin/metabolism; Transcription Factor CHOP; Transcription Factors/metabolism; Tunicamycin/metabolism

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

31156–31165

Issue

35

Volume

280

Citation

Yang Ling; Carlson Sara G; McBurney Denise; Horton Walter E Jr, “Multiple signals induce endoplasmic reticulum stress in both primary and immortalized chondrocytes resulting in loss of differentiation, impaired cell growth, and apoptosis.,” NEOMED Bibliography Database, accessed September 26, 2021, https://neomed.omeka.net/items/show/4071.

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