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| Research article summary (published 28 Dec 2008): |
Fibroblast growth factor receptor 2 promotes osteogenic differentiation in mesenchymal cells via ERK1/2 and protein kinase C signaling.
Full Abstract
Mesenchymal stem cells (MSCs) are able to differentiate into several lineages including osteoblasts. The signaling mechanisms involved in the osteogenic differentiation of MSCs are however not fully understood. We investigated the role of fibroblast growth factor receptor 2 (FGFR2) in osteoblast committment and differentiation of murine mesenchymal C3H10T1/2 cells stably transfected with wild type (WT) or activated FGFR2 due to Apert S252W genetic mutation (MT). WT FGFR2 slightly increased, whereas MT FGFR2 strongly increased, FGFR2 tyrosine phosphorylation, indicating activation of the receptor. WT and MT FGFR2 increased C3H10T1/2 cell proliferation but not survival. Both WT and MT FGFR2 increased early and late osteoblast gene expression and matrix mineralization. Forced expression of WT and MT FGFR2 also increased osteoblast gene expression in MC3T3-E1 calvaria osteoblasts. In both cell types, MT FGFR2 was more effective than WT FGFR2. In contrast, WT and MT FGFR2 decreased adipocyte differentiation of C3H10T1/2 cells. WT and MT FGFR2 induced ERK1/2 but not JNK or PI3K/AKT phosphorylation. MT, but not WT, also increased protein kinase C (PKC) activity. Pharmacological inhibition of ERK1/2 prevented cell proliferation induced by WT and MT FGFR2. Using dominant-negative ERK and PKCalpha vectors, we demonstrated that WT and MT FGFR2 promoted osteoblast gene expression through ERK1/2 and PKCalpha signaling, respectively. This study identifies FGFR2 as a novel regulatory molecule that promotes osteogenic differentiation in murine MSCs. The promoting effect of WT and MT FGFR2 is mediated by ERK1/2 and PKCalpha pathways that play essential and distinct roles in FGFR2-induced osteogenic differentiation of mesenchymal cells.
Author information
Author/s: Miraoui, Hichem (H); Oudina, Karim (K); Petite, Hervé (H); Tanimoto, Yukiho (Y); Moriyama, Keiji (K); Marie, Pierre J (PJ);
Affiliation: INSERM U606, Paris, France.
Journal and publication information
Publication Type: Journal Article; Research Support, Non-U.S. Gov't
Journal: The Journal of biological chemistry (J Biol Chem), published in United States. (Language: eng)
Reference: 2009-Feb; vol 284 (issue 8) : pp 4897-904
Dates: Created 2009/02/16; Completed 2009/04/13;
PMID: 19117954, status: MEDLINE (last retrieval date: 4/13/2009, IMS Date: 13 Apr 2009 00:00:00)
Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.
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