Ballarini, Elisa

Caldara, Cristina

Carini, Fabrizio

Donzelli, Elisabetta

Foudah, Dana

Miloso, Mariarosaria

Scuteri, Arianna

Tredici, Giovanni

Firenze University Press: E-Journals

IJAE Vol. 115, n. 1/2 (Supplement), 2010
59
ERK1 and ERK2 involvement in human Mesenchymal 
Stem Cells adipogenic differentiation
Elisabetta Donzelli, Elisa Ballarini, Arianna Scuteri, Dana Foudah, Cristina Caldara, Fabrizio Carini, 
Giovanni Tredici, Mariarosaria Miloso
 Dipartimento di Neuroscienze e Tecnologie Biomediche, Facoltà di Medicina e Chirurgia, Università degli Studi di 
Milano-Bicocca, Monza, Italia
Aims In order to develop therapeutic strategies to control obesity and the related 
pathologies, it is very important to deepen the knowledge of adipocytes biology and 
the mechanisms that control adipogenesis. In the present work we have studied the 
molecular mechanisms at the basis of the adipocytes differentiation using the human 
Mesenchymal Stem Cells (hMSCs), undifferentiated stem cells present in the bone mar-
row that are the physiological precursors of adipocytes in the organism. In particular we 
have focused our attention on the MAPKinases ERK1 and ERK2, that are involved in 
many biological and cellular processes. 
Methods hMSCs, obtained from iliac crest bone marrow, were induced to adipo-
genic differentiation by treatment with Adipogenic Induction Medium for 10 days (de-
termination phase), then replaced with Adipogenic Maintenance Medium until the end 
of treatment at day 28 (terminal differentiation phase). hMSC adipogenic differentia-
tion was evaluated by morphological and molecular techniques. Control cells were rep-
resented by hMSCs cultured in absence of adipogenic supplements. ERK1 and ERK2 
expression and phosphorylation were evaluated by immunoblotting experiments. The 
specific ERK inhibitor U0126 was added to the adipogenic medium at different times 
during the adipogenic differentiation protocol. 
Results hMSC treated with adipogenic differentiation protocol showed lipid drop-
lets that increased in number and size during the whole differentiation period. In treated 
hMSC both ERK1 and ERK2 phosphorylation was reduced in comparison to control 
hMSCs, but time and intensity of these reductions were different for the two isoforms. 
A decrease of the total amount of ERK1 was also observed. The presence of U0126 dur-
ing the whole differentiation period hampered the adipogenic differentiation of hMSCs, 
as very few hMSCs showed the appearance of lipid droplets that were reduced both in 
number and size. When U0126 was administered only during the determination phase 
the number of hMSCs recruited in the differentiation program was reduced, while when 
U0126 was administered only in the terminal differentiation phase, hMSCs did not ac-
quired a mature adipocytic phenotype.
Conclusion In this work we demonstrate that ERK1 and ERK2 are important for 
hMSC adipogenic differentiation. Our results suggest that ERK1 and ERK2 play a key 
role in determining how many cells enter into the adipogenic differentiation program 
and acquire the phenotipycal and molecular characteristics of mature adipocytes.
Key words
ERK, Mesenchymal Stem Cells, Adipogenic Differentiation, Adipocytes Biology, U0126


ERK1 and ERK2 involvement in human Mesenchymal Stem Cells adipogenic differentiation

http://www.fupress.net/index.php/ijae/article/download/8817/8206

ERK1 and ERK2 involvement in human Mesenchymal Stem Cells adipogenic differentiation

Abstract

Similar works

Full text

Available Versions

Firenze University Press: E-Journals