ERK1 and ERK2 are involved in recruitment and maturation of human mesenchymal stem cells induced to adipogenic differentiation

Abstract

Adipocytes' biology and the mechanisms that control adipogenesis have gained importance because of the need to develop therapeutic strategies to control obesity and the related pathologies. Human mesenchymal stem cells (hMSCs), undifferentiated stem cells present in the bone marrow that are physiological precursors of adipocytes, were induced to adipogenic differentiation. The molecular mechanisms on the basis of the adipogenesis were evaluated, focusing on the MAPKinases ERK1 and ERK2, which are involved in many biological and cellular processes. ERK1 and ERK2 phosphorylation was reduced with different timing and intensity for the two isoforms in treated hMSCs in comparison with control cells until day 10 and then at 14-28 days, it reached the level of untreated cultures. The total amount of ERK1 was also decreased up to day 10 and then was induced to the level of untreated cultures, whereas the expression of ERK2 was not changed following adipogenic induction. Treatment with the specific ERK1/2 inhibitor U0126 during the whole differentiation period hampered hMSCs' adipogenic differentiation, as lipid droplets appeared in very few cells and were reduced in number and size. When U0126 was administered only during the initial phase of differentiation, the number of hMSCs recruited to adipogenesis was reduced while, when it was administered later, hMSCs did not acquire a mature adipocytic phenotype. ERK1 and ERK2 are important for hMSC adipogenic differentiation since any alteration to the correct timing of their phosphorylation affects either the recruitment into the differentiation program and the extent of their maturation.

Power-Frequency Magnetic Field Inhibits Adipogenic Differentiation in Human ADSC

“…n = 7 experimental runs). Such changes in the expression of these proteins, being consistent with those observed in different cell types undergoing adipocyte differentiation in vitro [31,50,51], indicate that the selected markers may be suitable to the study of the potential influence of the MF on the adipogenesis of ADSC.…”

MiR-378a-3p enhances adipogenesis by targeting mitogen-activated protein kinase 1

“…MAPK1 also reportedly regulates adipogenesis [29,30]; however, its roles in this process are complicated. On the one hand, MAPK1 up-regulates the expression of crucial adipogenic regulators such as peroxisome proliferator-activated receptor c (PPARc) and the CCAAT-enhancer-binding proteins a, b, and d at the beginning of adipogenesis [31,32].…”

Extracellular regulated protein kinases 1/2 phosphorylation is required for hepatic differentiation of human umbilical cord-derived mesenchymal stem cells

“…[28][29][30] Inhibition of the ERK1/2 pathway can increase ALP activity, and that mineralization in skeletal muscle-derived stem cells leads to osteogenesis. 31 Hepatic differentiation is tightly regulated by cytokines and growth factors through signaling events.…”