Investigation of FGFR2-IIIC signaling via FGF-2 ligand for advancing GCT stromal cell differentiation
Authors: Isabella W Y Mak
Michelle Ghert
Mohini Singh
Shalini Singh
Robert Turcotte
Journal: PLoS ONE (2012)
Discipline: Multidisciplinary
Keywords: Giant cell tumor of bone; GCT; TWIST1; FGFR-2; osteoblastic differentiation
Affiliations: Department of Surgery, McMaster University, Hamilton, Ontario, Canada.

Abstract:  Giant cell tumor of bone (GCT) is an aggressive bone tumor consisting of multinucleated osteoclast-like giant cells and proliferating osteoblast-like stromal cells. The signaling mechanism involved in GCT stromal cell osteoblastic differentiation is not fully understood. Previous work in our lab reported that GCT stromal cells express high levels of TWIST1, a master transcription factor in skeletal development, which in turn down-regulates Runx2 expression and prevents terminal osteoblastic differentiation in these cells. The purpose of this study was to determine the upstream regulation of TWIST1 in GCT cells. Using GCT stromal cells obtained from patient specimens, we demonstrated that fibroblast growth factor receptor (FGFR)-2 signaling plays an essential role in bone development and promotes differentiation of immature osteoblastic cells. Fibroblast growth factor (FGF)-2 stimulates FGFR-2 expression, resulting in decreased TWIST1 expression and increased Runx2, alkaline phosphastase (ALP) and osteopontin (OPN) expression. Inhibition of FGFR-2 through siRNA decreased the expression of ALP, Runx2 and OPN in GCT stromal cells. Our study also confirmed that FGF-2 ligand activates downstream ERK1/2 signaling and pharmacological inhibition of the ERK1/2 signaling pathway suppresses FGF-2 stimulated osteogenic differentiation in these cells. Our results indicate a significant role of FGFR-2 signaling in osteoblastic differentiation in GCT stromal cells. 

Retracted: Yes

PubPeer comments:
 Thank-you for pointing out this error! We have contacted PlosONE and a review is underway in conjunction with the journal and the first author regarding the raw data and the original blots. Once the review is complete, the journal will decide the course of action. Thank-you again for taking the time to review and provide feedback. We are very happy to have the opportunity to correct! , 
 Fig 7a https: imgur.com a dsXu86B , 
 2019 retraction. https: journals.plos.org plosone article?id=10.1371 journal.pone.0220356 After the publication of this article [1], concerns were raised that Actin panel lanes 3, 4 in Fig 7A appear similar to lanes 5, 6. The authors explained that this duplication was due to an error during figure preparation and provided an updated figure along with the original, underlying images to the journal. The underlying images provided did not fully match the updated figure thus not resolving the concerns satisfactorily. A member of our Editorial Board concluded that the updated figure did not support p-ERK 1 2 activation as described in the results. In light of the unresolved concerns that question the validity of the findings, the PLOS ONE Editors retract this article. SS, MS, RT, MG agreed with retraction. IWYM did not respond. Reference 1. Singh S, Singh M, Mak IWY, Turcotte R, Ghert M (2012) Investigation of FGFR2-IIIC Signaling via FGF-2 Ligand for Advancing GCT Stromal Cell Differentiation. PLoS ONE 7(10): e46769. https: doi.org 10.1371 journal.pone.0046769 pmid:23071632 ,