In vitro expansion affects the response of chondrocytes to mechanical simulation

Journal article (2007)

Authors

RHJ Das External organisation
H Jahr External organisation
JAN Verhaar External organisation
JC van der Linden Computational Design and Mechanics - Mechanical, Maritime and Materials Engineering
GJVM Osch External organisation
H Weinans External organisation
Research Group
Computational Design and Mechanics (Mechanical, Maritime and Materials Engineering) (TU Delft)
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Published Date

2007

Language

Undefined/Unknown

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Faculty

Mechanical, Maritime and Materials Engineering

Department

Precision and Microsystems Engineering

Research Group

Computational Design and Mechanics

Abstract

Objective
Expansion of autologous chondrocytes is a common step in procedures for cartilage defect repair. Subsequent dedifferentiation can alter cellular response to mechanical loading, having major consequences for the cell's behavior in vivo after reimplantation. Therefore, we examined the response of primary and expanded human articular chondrocytes to mechanical loading.

Method
Primary and expanded chondrocytes were stretched at either 0.5% or 3.0% at 0.5 Hz, 2 h per day, for 3 days. Gene expression levels of matrix components (aggrecan (AGC1), lubricin (PRG4), collagen type I (COL1), type II (COL2) and type X (COL10)) as well as matrix enzymes (matrix metalloproteinase 1 (MMP1), MMP3, MMP13) and SOX9 were compared to unstretched controls. To evaluate the effect of a chondrogenic environment on cellular response to stretch, redifferentiation medium was used on expanded cells.

Results
In primary chondrocytes, stretch led to mild decreases in AGC1, COL1 and COL10 gene expression (maximum of 3.8-fold) and an up-regulation of PRG4 (2.0-fold). In expanded chondrocytes, expression was down-regulated for AGC1 (up to 21-fold), PRG4 (up to 5.0-fold), COL1 (10-fold) and COL2 (2.9-fold). Also, expression was up-regulated for MMP1 (20-fold) and MMP3 (up to 4-fold), while MMP13 was down-regulated (2.8-fold). A chondrogenic environment appeared to temper effects of stretch.

Discussion
Our results show that expansion alters the response of human chondrocytes to stretch. Expanded chondrocytes greatly decrease gene expression of matrix constituents and increase expression of MMPs, whereas primary chondrocytes hardly respond. Our data could be a reference for optimization of cell sources or expansion protocols for reimplanted chondrocytes.

Key words: Cell culture; Mechanical loading; Chondrocyte phenotype; Dedifferentiation; Gene expression; Cell deformation; Stretch; Tissue engineering