title: Duration and magnitude of extracellular signal-regulated protein kinase phosphorylation determine adipogenesis or osteogenesis in human bone marrow-derived stem cells.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Ho Sun
authors.initials: HS
authors.lastname: Jung
authors.forename: Yun Hee
authors.initials: YH
authors.lastname: Kim
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Lee
mesh_terms: D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D000328:Adult; D000813:Anilides / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002070:Butadienes / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000494:pharmacology; D010012:Osteogenesis / Q000187:drug effects* / Q000235:genetics; D047495:PPAR gamma / Q000819:agonists / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D002070:Butadienes; D002839:Chromans; D009570:Nitriles; D047495:PPAR gamma; D045162:Thiazolidinediones; C113580:U 0126; D048049:Extracellular Signal-Regulated MAP Kinases; D000077288:Troglitazone