PMID- 18378228
OWN - NLM
STAT- MEDLINE
DCOM- 20080619
LR  - 20181201
IS  - 0014-4827 (Print)
IS  - 0014-4827 (Linking)
VI  - 314
IP  - 8
DP  - 2008 May 1
TI  - ERK2 protein regulates the proliferation of human mesenchymal stem cells without 
      affecting their mobilization and differentiation potential.
PG  - 1777-88
LID - 10.1016/j.yexcr.2008.01.020 [doi]
AB  - Human Mesenchymal Stem Cells (hMSC), derived mainly from adult bone marrow, are 
      valuable models for the study of processes involved in stem cell self-renewal and 
      differentiation. As the Extracellular signal-Regulated Kinase (ERK) signalling 
      pathway is a major contributor to cellular growth, differentiation and survival, 
      we have studied the functions of this kinase in hMSC activity. Ablation of ERK2 
      gene expression (but not ERK1) by RNA interference significantly reduced 
      proliferation of hMSC. This reduction was due to a defect in Cyclin D1 expression 
      and subsequent arrest in the G0/G1 phase of the cell cycle. hMSC growth is 
      enhanced through culture medium supplementation with growth factors (GFs) such as 
      Platelet-Derived Growth Factor (PDGF), basic Fibroblast Growth Factor (bFGF) or 
      Epidermal Growth Factor (EGF). However, these supplements could not rescue the 
      defect observed after ERK2 knockdown, suggesting a common signalling pathway used 
      by these GFs for proliferation. In contrast, ERK1/2 may be dissociated from 
      chemotactic signalling induced by the same GFs. Additionally, hMSCs were capable 
      of differentiating into adipocytes even in the absence of either ERK1 or ERK2 
      proteins. Our data show that hMSCs do not require cell division to enter the 
      adipogenic differentiation process, indicating that clonal amplification of these 
      cells is not a critical step. However, cell-cell contact seems to be an essential 
      requirement to be able to differentiate into mature adipocytes.
FAU - Carcamo-Orive, Ivan
AU  - Carcamo-Orive I
AD  - Fundacion Inbiomed, Foundation for Stem Cell Research, Mesenchymal Stem Cell 
      Department, Paseo Mikeletegi, 61 Bajo 20009, San Sebastian, Spain.
FAU - Tejados, Naiara
AU  - Tejados N
FAU - Delgado, Jesus
AU  - Delgado J
FAU - Gaztelumendi, Ainhoa
AU  - Gaztelumendi A
FAU - Otaegui, David
AU  - Otaegui D
FAU - Lang, Valerie
AU  - Lang V
FAU - Trigueros, Cesar
AU  - Trigueros C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080206
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
SB  - IM
MH  - Adipogenesis
MH  - Cell Differentiation
MH  - Cell Movement/drug effects
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/pharmacology
MH  - Mesenchymal Stem Cells/cytology/*enzymology/physiology
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/genetics/*physiology
MH  - Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/genetics
MH  - RNA Interference
EDAT- 2008/04/02 09:00
MHDA- 2008/06/20 09:00
CRDT- 2008/04/02 09:00
PHST- 2007/10/14 00:00 [received]
PHST- 2008/01/18 00:00 [revised]
PHST- 2008/01/23 00:00 [accepted]
PHST- 2008/04/02 09:00 [pubmed]
PHST- 2008/06/20 09:00 [medline]
PHST- 2008/04/02 09:00 [entrez]
AID - S0014-4827(08)00053-0 [pii]
AID - 10.1016/j.yexcr.2008.01.020 [doi]
PST - ppublish
SO  - Exp Cell Res. 2008 May 1;314(8):1777-88. doi: 10.1016/j.yexcr.2008.01.020. Epub 
      2008 Feb 6.