ERK2 protein regulates the proliferation of human mesenchymal stem cells without affecting their mobilization and differentiation potential

Iván Cárcamo-Orive, Naiara Tejados, Jesus Delgado-Calle, Ainhoa Gaztelumendi, David Otaegui, Valerie Lang, César Trigueros

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1777-1788
Number of pages12
JournalExperimental Cell Research
Volume314
Issue number8
DOIs
StatePublished - May 1 2008
Externally publishedYes

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Mesenchymal Stromal Cells
Intercellular Signaling Peptides and Proteins
Adipocytes
Proteins
Cell Cycle Resting Phase
Cyclin D1
Platelet-Derived Growth Factor
Extracellular Signal-Regulated MAP Kinases
G1 Phase
Fibroblast Growth Factor 2
Growth
RNA Interference
Epidermal Growth Factor
Cell Division
Culture Media
Cell Cycle
Phosphotransferases
Bone Marrow
Gene Expression
Survival

Keywords

  • Adipogenesis
  • Extracellular signal-Regulated Kinase
  • Growth factors
  • Human mesenchymal stem cell
  • RNA interference

ASJC Scopus subject areas

  • Cell Biology

Cite this

ERK2 protein regulates the proliferation of human mesenchymal stem cells without affecting their mobilization and differentiation potential. / Cárcamo-Orive, Iván; Tejados, Naiara; Delgado-Calle, Jesus; Gaztelumendi, Ainhoa; Otaegui, David; Lang, Valerie; Trigueros, César.

In: Experimental Cell Research, Vol. 314, No. 8, 01.05.2008, p. 1777-1788.

Research output: Contribution to journalArticle

Cárcamo-Orive, Iván ; Tejados, Naiara ; Delgado-Calle, Jesus ; Gaztelumendi, Ainhoa ; Otaegui, David ; Lang, Valerie ; Trigueros, César. / ERK2 protein regulates the proliferation of human mesenchymal stem cells without affecting their mobilization and differentiation potential. In: Experimental Cell Research. 2008 ; Vol. 314, No. 8. pp. 1777-1788.
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