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Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 J+Cell+Mol+Med 2010 ; 14 (6a): 1338-46 Nephropedia Template TP
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Mechanical load modulates chondrogenesis of human mesenchymal stem cells through the TGF-? pathway #MMPMID19432813
Li Z; Kupcsik L; Yao SJ; Alini M; Stoddart MJ
J Cell Mol Med 2010[Jun]; 14 (6a): 1338-46 PMID19432813show ga
This study investigated the effect of mechanical load on human mesenchymal stem cell (hMSC) differentiation under different exogenous transforming growth factor-?1 (TGF-?1) concentrations (0, 1 or 10 ng/ml).The role of the TGF-? signalling pathway in this process was also studied. Human MSCs were seeded into fibrin-biodegradable polyurethane scaffolds at a cell density of 5 × 106 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-?1 in the culture medium was sufficient to induce chondrogenesis of hMSCs. Depending on the TGF-?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-?1 concentrations. With TGF-?1 absent in the culture medium, mechanical load stimulated gene transcripts and protein synthesis of TGF-?1 and TGF-?3. TGF-? type I receptor inhibitor LY364947 blocked the up-regulation on TGF-?1 and TGF-?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-? pathway by up-regulating TGF-? gene expression and protein synthesis.