Duration and magnitude of extracellular signal-regulated protein kinase phosphorylation determine adipogenesis or osteogenesis in human bone marrow-derived stem cells

Yonsei Med J. 2011 Jan;52(1):165-72. doi: 10.3349/ymj.2011.52.1.165.

Abstract

Purpose: Imbalances between osteogenic and adipogenic differentiation leads to diseases such as osteoporosis. The aim of our study was to demonstrate the differences in extracellular signal-regulated kinase (ERK) phosphorylation during both adipogenesis and osteogenesis of human bone marrow-derived stem cells (BMSCs).

Materials and methods: Using troglitazone, GW9662 and U0126, we investigated their role in hBMSC differentiation to adipogenic and osteogenic fates.

Results: ERK1/2 inhibition by U0126 suppressed proliferator-activated receptor (PPAR)γ expression and lipid accumulation, while it decreased the mRNA expression of adipogenic genes (lipoprotein lipase, PPARγ, and adipocyte protein) and osteogenic genes (type I collagen and osteopontin). ERK phosphorylation was transient and decreased during adipogenesis, whereas it occurred steadily during osteogenesis. Troglitazone, a PPARγ agonist, induced adipogenesis by inhibiting ERK phosphorylation even in an osteogenic medium, suggesting that ERK signaling needs to be shut off in order to proceed with adipose cell commitment. Cell proliferation was greatly increased in osteogenesis but was not changed during adipogenesis, indicating that ERK might play different roles in cellular proliferation and differentiation between the two committed cell types.

Conclusion: The duration and magnitude of ERK activation might be a crucial factor for the balance between adipogenesis and osteogenesis in human bone marrow-derived stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipogenesis / drug effects*
  • Adipogenesis / genetics
  • Adult
  • Anilides / pharmacology
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Butadienes / pharmacology
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Chromans / pharmacology
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nitriles / pharmacology
  • Osteogenesis / drug effects*
  • Osteogenesis / genetics
  • PPAR gamma / agonists
  • PPAR gamma / antagonists & inhibitors
  • Phosphorylation / drug effects
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / metabolism*
  • Thiazolidinediones / pharmacology
  • Troglitazone

Substances

  • 2-chloro-5-nitrobenzanilide
  • Anilides
  • Butadienes
  • Chromans
  • Nitriles
  • PPAR gamma
  • Thiazolidinediones
  • U 0126
  • Extracellular Signal-Regulated MAP Kinases
  • Troglitazone