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The present study aimed to elucidate whether extracellular signal-regulated kinases 1/2 (ERK1/2) and p38 mitogen-activated protein kinases pathways participate in the transduction of mechanical stretch exerted on adipose stem cells (ASCs) into intracellular osteogenic signals, and if so whether both pathways have time-dependent feature. Rat ASCs were cultured in osteogenic medium for 72 h and assigned into three sets, namely ERK1/2 inhibitor treated set, p38 inhibitor treated set, and the control set. After inhibitor treatment, all cells were subjected to cyclic stretch(2000 με, 1 Hz) on a four-point bending mechanical loading device. Protein and mRNA samples were acquired at six time points: 0, 15 min, 30 min, 1 h, 2 h and 6 h. Western blot showed phosphorylation level of ERK1/2 was elevated by cyclic tensile stress at all time points, while p38 at 15 min, 30 min and 1 h, and the elevation can be completely blocked by corresponding inhibitors. The treatment by ERK1/2 inhibitor was shown to antagonize the up-regulation of osteogenic genes bone morphogenetic protein 2 (BMP-2) and runt-related transcription factor 2 (Runx2) by mechanical stretch at 15 min and 6 h, whereas p38 inhibitor took effect at 15 min only. The results suggested both ERK and p38 could be positive mediators of stretch-induced osteogenic differentiation of ASCs, and ERK stimulate the stretch-induced osteogenic differentiation at both early and late stages while p38 responds to mechanical stretch in a more rapid fashion.
This article was published in the following journal.
Name: Stem cell research
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The maximum stress a material subjected to a stretching load can withstand without tearing. (McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed, p2001)
A fibril-associated collagen found in many tissues bearing high tensile stress, such as TENDONS and LIGAMENTS. It is comprised of a trimer of three identical alpha1(XII) chains.
The malignant stem cells of TERATOCARCINOMAS, which resemble pluripotent stem cells of the BLASTOCYST INNER CELL MASS. The EC cells can be grown in vitro, and experimentally induced to differentiate. They are used as a model system for studying early embryonic cell differentiation.
A forkhead box transcription factor that is a major target of INSULIN signaling and regulator of metabolic homeostasis in response to OXIDATIVE STRESS. It binds to the insulin RESPONSE ELEMENT (IRE) and the related Daf-16 family binding element (DBE). Its activity is suppressed by insulin and it also regulates OSTEOBLAST proliferation, controls bone mass, and skeletal regulation of GLUCOSE metabolism. It promotes GLUCONEOGENESIS in HEPATOCYTES and regulates gene expression in ADIPOSE TISSUE. It is also an important CELL DEATH regulator. Chromosomal aberrations involving the FOXO1 gene occur in RHABDOMYOSARCOMA.
A growth differentiation factor that may play a role in maintaining the undifferentiated state of PLURIPOTENT STEM CELLS by inhibiting the actions of BONE MORPHOGENETIC PROTEINS. Differentiation factor 3 is also considered a nodal signaling ligand that influences the genesis of left-right asymmetry.
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