PMID- 21155050 OWN - NLM STAT- MEDLINE DCOM- 20110503 LR - 20211020 IS - 1976-2437 (Electronic) IS - 0513-5796 (Print) IS - 0513-5796 (Linking) VI - 52 IP - 1 DP - 2011 Jan TI - Duration and magnitude of extracellular signal-regulated protein kinase phosphorylation determine adipogenesis or osteogenesis in human bone marrow-derived stem cells. PG - 165-72 LID - 10.3349/ymj.2011.52.1.165 [doi] AB - 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)gamma expression and lipid accumulation, while it decreased the mRNA expression of adipogenic genes (lipoprotein lipase, PPARgamma, 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 PPARgamma 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. FAU - Jung, Ho Sun AU - Jung HS AD - Department of Orthopaedic Surgery, Yonsei University College of Medicine, Seoul, Korea. FAU - Kim, Yun Hee AU - Kim YH FAU - Lee, Jin Woo AU - Lee JW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Korea (South) TA - Yonsei Med J JT - Yonsei medical journal JID - 0414003 RN - 0 (2-chloro-5-nitrobenzanilide) RN - 0 (Anilides) RN - 0 (Butadienes) RN - 0 (Chromans) RN - 0 (Nitriles) RN - 0 (PPAR gamma) RN - 0 (Thiazolidinediones) RN - 0 (U 0126) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - I66ZZ0ZN0E (Troglitazone) SB - IM MH - Adipogenesis/*drug effects/genetics MH - Adult MH - Anilides/pharmacology MH - Bone Marrow Cells/*cytology/drug effects/metabolism MH - Butadienes/pharmacology MH - Cell Differentiation/drug effects MH - Cells, Cultured MH - Chromans/pharmacology MH - Extracellular Signal-Regulated MAP Kinases/*metabolism MH - Female MH - Humans MH - Male MH - Middle Aged MH - Nitriles/pharmacology MH - Osteogenesis/*drug effects/genetics MH - PPAR gamma/agonists/antagonists & inhibitors MH - Phosphorylation/drug effects MH - Reverse Transcriptase Polymerase Chain Reaction MH - Stem Cells/*cytology/drug effects/*metabolism MH - Thiazolidinediones/pharmacology MH - Troglitazone PMC - PMC3017693 COIS- The authors have no financial conflicts of interest. EDAT- 2010/12/15 06:00 MHDA- 2011/05/04 06:00 PMCR- 2011/01/01 CRDT- 2010/12/15 06:00 PHST- 2010/12/15 06:00 [entrez] PHST- 2010/12/15 06:00 [pubmed] PHST- 2011/05/04 06:00 [medline] PHST- 2011/01/01 00:00 [pmc-release] AID - 201101165 [pii] AID - 10.3349/ymj.2011.52.1.165 [doi] PST - ppublish SO - Yonsei Med J. 2011 Jan;52(1):165-72. doi: 10.3349/ymj.2011.52.1.165.