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Stem Cells. 2004;22(3):313-23.

Effects of cyclic compressive loading on chondrogenesis of rabbit bone-marrow derived mesenchymal stem cells.

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Research Service and Geriatrics Research, Education, and Clinical Center, Veterans Affairs Medical Center, Miami, Florida 33125, USA.


The objective of this study was to examine the effects of cyclic compressive loading on chondrogenic differentiation of rabbit bone-marrow mesenchymal stem cells (BM-MSCs) in agarose cultures. Rabbit BM-MSCs were obtained from the tibias and femurs of New Zealand white rabbits. After the chondrogenic potential of BM-MSCs was verified by pellet cultures, cell-agarose constructs were made by suspending BM-MSCs in 2% agarose (10(7) cells/ml) for a cyclic, unconfined compression test performed in a custom-made bioreactor. Specimens were divided into four groups: control; transforming growth factor (TGF-beta) (with TGF-beta1 treatment); loading (with stimulation of cyclic, unconfined compressive loading); and TGF-beta loading (with TGF-beta1 treatment and loading stimulation) groups. In the loading experiment, specimens were subjected to sinusoidal loading with a 10% strain magnitude at a frequency of 1 Hz for 4 hours a day. Experiments were conducted for 3, 7, and 14 consecutive days. While the experimental groups (TGF-beta, loading, and TGF-beta loading) exhibited significantly higher levels of expressions of chondrogenic markers (collagen II and aggrecan) at three time periods, there were no differences among the experimental groups after an extra 5-day culture. This suggests that compressive loading alone induces chondrogenic differentiation of rabbit BM-MSCs as effectively as TGF-beta or TGF-beta plus loading treatment. Moreover, both the compressive loading and the TGF-beta1 treatment were found to promote the TGF-beta1 gene expression of rabbit BM-MSCs. These findings suggest that cyclic compressive loading can promote the chondrogenesis of rabbit BM-MSCs by inducing the synthesis of TGF-beta1, which can stimulate the BM-MSCs to differentiate into chondrocytes.

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