Effect of adipose-derived stem cells modified by insulin-like growth factor I gene on TWEAK/Fn14 signaling pathway / 中国组织工程研究

ABSTRACT

BACKGROUND:Because insulin-like growth factor I has the ability to induce mesenchymal stem cells into chondrocytes, we hypothesized that the chondrogenic diferentiation of adipose-derived stem cels can be improvedvia insulin-like growth factor I transfection. OBJECTIVE:To investigate the influence of insulin-like growth factor I transfection on chondrogenic potential of adipose-derived stem cels in vitroand tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible 14 (Fn14) signaling pathway. METHODS:Recombinant lentivirus plasmid pLVX-IGF-I-IRES-ZsGreenl was constructed and transferred into passage 3 adipose-derived stem cels, and then these stem cels were induced to diferentiate into chondrocytes (experimental group 1). Meanwhile, the cels transfected with pLVX-IRES-ZsGreenl were taken as green fluorescent protein/adipose mesenchymal stem cel group (experimental group 2), and those with no transfection acted as control group. RESULTS AND CONCLUSION:The mRNA expression of TWEAK was reduced in the experimental group 1 as compared with the other two groups, but the mRNA expressions of insulin-like growth factor I, Col2a1 and Sox9 were up-regulated in the experimental group 1. At the same time, the protein expression of matrix metaloproteinase-3 and TWEAK were down-regulated, while the protein expression of Col2a1 was increased in the insulin-like growth factor I-transfected cels in contrast to the cels modified with pLVX-IRES-ZsGreenl or with no transfection. These findings indicate that pLVX-IGF-I-IRES-ZsGreenl transfection of adipose-derived stem cels results in a higher expression of insulin-like growth factor I, and down-regulates the expression of TWEAK mRNA and protein, which improves the diferentiation of adipose-derived mesenchymal stem cels into chondrocytes.