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2010 ; 14
(6A
): 1338-46
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Mechanical load modulates chondrogenesis of human mesenchymal stem cells through
the TGF-beta pathway
#MMPMID19432813
Li Z
; Kupcsik L
; Yao SJ
; Alini M
; Stoddart MJ
J Cell Mol Med
2010[Jun]; 14
(6A
): 1338-46
PMID19432813
show ga
This study investigated the effect of mechanical load on human mesenchymal stem
cell (hMSC) differentiation under different exogenous transforming growth
factor-beta1 (TGF-beta(1)) concentrations (0, 1 or 10 ng/ml).The role of the
TGF-beta signalling pathway in this process was also studied. Human MSCs were
seeded into fibrin-biodegradable polyurethane scaffolds at a cell density of 5 x
10(6) cells per scaffold and stimulated using our bioreactor. One hour of surface
motion superimposed on cyclic compression was applied once a day over seven
consecutive days. Scaffolds were analysed for gene expression, DNA content and
glycosaminoglycan amount. Addition of TGF-beta(1) in the culture medium was
sufficient to induce chondrogenesis of hMSCs. Depending on the TGF-beta(1)
concentration of the culture medium, mechanical load stimulated chondrogenesis of
hMSCs compared to the unloaded scaffolds, with a much stronger effect on gene
expression at lower TGF-beta(1) concentrations. With TGF-beta(1) absent in the
culture medium, mechanical load stimulated gene transcripts and protein synthesis
of TGF-beta(1) and TGF-beta(3). TGF-beta type I receptor inhibitor LY364947
blocked the up-regulation on TGF-beta(1) and TGF-beta(3) production stimulated by
mechanical load, and also blocked the chondrogenesis of hMSCs. Taken together,
these findings suggest that mechanical load promotes chondrogenesis of hMSCs
through TGF-beta pathway by up-regulating TGF-beta gene expression and protein
synthesis.