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Arthritis Research & Therapy
Published in: Arthritis Research & Therapy 3/2010

Open Access 01-06-2010 | Research article

Physiological tonicity improves human chondrogenic marker expression through nuclear factor of activated T-cells 5 in vitro

Authors: Anna E van der Windt, Esther Haak, Ruud HJ Das, Nicole Kops, Tim JM Welting, Marjolein MJ Caron, Niek P van Til, Jan AN Verhaar, Harrie Weinans, Holger Jahr

Published in: Arthritis Research & Therapy | Issue 3/2010

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Abstract

Introduction

Chondrocytes experience a hypertonic environment compared with plasma (280 mOsm) due to the high fixed negative charge density of cartilage. Standard isolation of chondrocytes removes their hypertonic matrix, exposing them to nonphysiological conditions. During in vitro expansion, chondrocytes quickly lose their specialized phenotype, making them inappropriate for cell-based regenerative strategies. We aimed to elucidate the effects of tonicity during isolation and in vitro expansion on chondrocyte phenotype.

Methods

Human articular chondrocytes were isolated and subsequently expanded at control tonicity (280 mOsm) or at moderately elevated, physiological tonicity (380 mOsm). The effects of physiological tonicity on chondrocyte proliferation and chondrogenic marker expression were evaluated. The role of Tonicity-responsive Enhancer Binding Protein in response to physiological tonicity was investigated using nuclear factor of activated T-cells 5 (NFAT5) RNA interference.

Results

Moderately elevated, physiological tonicity (380 mOsm) did not affect chondrocyte proliferation, while higher tonicities inhibited proliferation and diminished cell viability. Physiological tonicity improved expression of chondrogenic markers and NFAT5 and its target genes, while suppressing dedifferentiation marker collagen type I and improving type II/type I expression ratios >100-fold. Effects of physiological tonicity were similar in osteoarthritic and normal (nonosteoarthritic) chondrocytes, indicating a disease-independent mechanism. NFAT5 RNA interference abolished tonicity-mediated effects and revealed that NFAT5 positively regulates collagen type II expression, while suppressing type I.

Conclusions

Physiological tonicity provides a simple, yet effective, means to improve phenotypical characteristics during cytokine-free isolation and in vitro expansion of human articular chondrocytes. Our findings will lead to the development of improved cell-based repair strategies for chondral lesions and provides important insights into mechanisms underlying osteoarthritic progression.
Appendix
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Metadata
Title
Physiological tonicity improves human chondrogenic marker expression through nuclear factor of activated T-cells 5 in vitro
Authors
Anna E van der Windt
Esther Haak
Ruud HJ Das
Nicole Kops
Tim JM Welting
Marjolein MJ Caron
Niek P van Til
Jan AN Verhaar
Harrie Weinans
Holger Jahr
Publication date
01-06-2010
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 3/2010
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar3031

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Keynote webinar | Spotlight on medication adherence

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Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

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A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
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