Effects of cyclic compressive loading on chondrogenesis of rabbit bone-marrow derived mesenchymal stem cells.
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.
Huang
C-Y Charles
CY
Research Service and Geriatrics Research, Education, and Clinical Center, Veterans Affairs Medical Center, Miami, Florida 33125, USA.
Hagar
Kristen L
KL
Frost
Lauren E
LE
Sun
Yubo
Y
Cheung
Herman S
HS
D053674:Aggrecans; D000818:Animals; D019149:Bioreactors; D001854:Bone Marrow Cells / Q000502:physiology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects / Q000502:physiology*; D024043:Collagen Type II / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D037181:Lectins, C-Type; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D011509:Proteoglycans / Q000378:metabolism; D011817:Rabbits; D012685:Sepharose / Q000737:chemistry; D013314:Stress, Mechanical; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D053674:Aggrecans; D024043:Collagen Type II; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; D012685:Sepharose