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Fibroblast growth factor receptor 2 promotes osteogenic differentiation in mesenchymal cells via ERK1/2 and protein kinase C signaling.
J Biol Chem. 2009 Feb 20; 284(8):4897-904.JB

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.

Authors+Show Affiliations

INSERM U606, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19117954

Citation

Miraoui, Hichem, et al. "Fibroblast Growth Factor Receptor 2 Promotes Osteogenic Differentiation in Mesenchymal Cells Via ERK1/2 and Protein Kinase C Signaling." The Journal of Biological Chemistry, vol. 284, no. 8, 2009, pp. 4897-904.
Miraoui H, Oudina K, Petite H, et al. Fibroblast growth factor receptor 2 promotes osteogenic differentiation in mesenchymal cells via ERK1/2 and protein kinase C signaling. J Biol Chem. 2009;284(8):4897-904.
Miraoui, H., Oudina, K., Petite, H., Tanimoto, Y., Moriyama, K., & Marie, P. J. (2009). Fibroblast growth factor receptor 2 promotes osteogenic differentiation in mesenchymal cells via ERK1/2 and protein kinase C signaling. The Journal of Biological Chemistry, 284(8), 4897-904. https://doi.org/10.1074/jbc.M805432200
Miraoui H, et al. Fibroblast Growth Factor Receptor 2 Promotes Osteogenic Differentiation in Mesenchymal Cells Via ERK1/2 and Protein Kinase C Signaling. J Biol Chem. 2009 Feb 20;284(8):4897-904. PubMed PMID: 19117954.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fibroblast growth factor receptor 2 promotes osteogenic differentiation in mesenchymal cells via ERK1/2 and protein kinase C signaling. AU - Miraoui,Hichem, AU - Oudina,Karim, AU - Petite,Hervé, AU - Tanimoto,Yukiho, AU - Moriyama,Keiji, AU - Marie,Pierre J, Y1 - 2008/12/30/ PY - 2009/1/2/entrez PY - 2009/1/2/pubmed PY - 2009/4/14/medline SP - 4897 EP - 904 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 284 IS - 8 N2 - 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. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/19117954/Fibroblast_growth_factor_receptor_2_promotes_osteogenic_differentiation_in_mesenchymal_cells_via_ERK1/2_and_protein_kinase_C_signaling_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=19117954 DB - PRIME DP - Unbound Medicine ER -