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Title: Fibroblast growth factor 2 inhibits up-regulation of bone morphogenic proteins and their receptors during osteoblastic differentiation of human mesenchymal stem cells

Abstract

Highlights: Black-Right-Pointing-Pointer FGF modulates BMPs pathway in HMSCs by down-regulating BMP/BMPR expression. Black-Right-Pointing-Pointer This effect is mediated by ERK and JNK MAPKs pathways. Black-Right-Pointing-Pointer Crosstalk between FGF and BMPs must be taken into account in skeletal bioengineering. Black-Right-Pointing-Pointer It must also be considered in the use of recombinant BMPs in orthopedic and spine surgeries. -- Abstract: Understanding the interactions between growth factors and bone morphogenic proteins (BMPs) signaling remains a crucial issue to optimize the use of human mesenchymal stem cells (HMSCs) and BMPs in therapeutic perspectives and bone tissue engineering. BMPs are potent inducers of osteoblastic differentiation. They exert their actions via BMP receptors (BMPR), including BMPR1A, BMPR1B and BMPR2. Fibroblast growth factor 2 (FGF2) is expressed by cells of the osteoblastic lineage, increases their proliferation and is secreted during the healing process of fractures or in surgery bone sites. We hypothesized that FGF2 might influence HMSC osteoblastic differentiation by modulating expressions of BMPs and their receptors. BMP2, BMP4, BMPR1A and mainly BMPR1B expressions were up-regulated during this differentiation. FGF2 inhibited HMSCs osteoblastic differentiation and the up-regulation of BMPs and BMPR. This effect was prevented by inhibiting the ERK or JNK mitogen-activated protein kinases which are known to bemore » activated by FGF2. These data provide a mechanism explaining the inhibitory effect of FGF2 on osteoblastic differentiation of HMSCs. These crosstalks between growth and osteogenic factors should be considered in the use of recombinant BMPs in therapeutic purpose of fracture repair or skeletal bioengineering.« less

Authors:
 [1];  [2];  [3];  [1];  [2];  [4];  [1];  [2];  [1];  [4];  [1]
  1. Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoleon, BP120, 62327 Boulogne sur Mer (France)
  2. (France)
  3. (Switzerland)
  4. Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14 (Switzerland)
Publication Date:
OSTI Identifier:
22210316
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 427; Journal Issue: 4; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BONE TISSUES; CELL PROLIFERATION; FIBROBLASTS; FRACTURES; GROWTH FACTORS; HEALING; PHOSPHOTRANSFERASES; RECEPTORS; STEM CELLS; SURGERY; VERTEBRAE

Citation Formats

Biver, Emmanuel, E-mail: ebiver@yahoo.fr, Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex, Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14, Soubrier, Anne-Sophie, Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex, Thouverey, Cyril, Cortet, Bernard, Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex, Broux, Odile, Caverzasio, Joseph, and Hardouin, Pierre. Fibroblast growth factor 2 inhibits up-regulation of bone morphogenic proteins and their receptors during osteoblastic differentiation of human mesenchymal stem cells. United States: N. p., 2012. Web. doi:10.1016/J.BBRC.2012.09.129.
Biver, Emmanuel, E-mail: ebiver@yahoo.fr, Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex, Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14, Soubrier, Anne-Sophie, Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex, Thouverey, Cyril, Cortet, Bernard, Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex, Broux, Odile, Caverzasio, Joseph, & Hardouin, Pierre. Fibroblast growth factor 2 inhibits up-regulation of bone morphogenic proteins and their receptors during osteoblastic differentiation of human mesenchymal stem cells. United States. doi:10.1016/J.BBRC.2012.09.129.
Biver, Emmanuel, E-mail: ebiver@yahoo.fr, Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex, Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14, Soubrier, Anne-Sophie, Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex, Thouverey, Cyril, Cortet, Bernard, Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex, Broux, Odile, Caverzasio, Joseph, and Hardouin, Pierre. Fri . "Fibroblast growth factor 2 inhibits up-regulation of bone morphogenic proteins and their receptors during osteoblastic differentiation of human mesenchymal stem cells". United States. doi:10.1016/J.BBRC.2012.09.129.
@article{osti_22210316,
title = {Fibroblast growth factor 2 inhibits up-regulation of bone morphogenic proteins and their receptors during osteoblastic differentiation of human mesenchymal stem cells},
author = {Biver, Emmanuel, E-mail: ebiver@yahoo.fr and Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex and Service of Bone Diseases, Department of Internal Medicine Specialties, University Hospital of Geneva, CH-1211 Geneva 14 and Soubrier, Anne-Sophie and Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex and Thouverey, Cyril and Cortet, Bernard and Department of Rheumatology, Lille University Hospital, Roger Salengro Hospital, 59037 Lille cedex and Broux, Odile and Caverzasio, Joseph and Hardouin, Pierre},
abstractNote = {Highlights: Black-Right-Pointing-Pointer FGF modulates BMPs pathway in HMSCs by down-regulating BMP/BMPR expression. Black-Right-Pointing-Pointer This effect is mediated by ERK and JNK MAPKs pathways. Black-Right-Pointing-Pointer Crosstalk between FGF and BMPs must be taken into account in skeletal bioengineering. Black-Right-Pointing-Pointer It must also be considered in the use of recombinant BMPs in orthopedic and spine surgeries. -- Abstract: Understanding the interactions between growth factors and bone morphogenic proteins (BMPs) signaling remains a crucial issue to optimize the use of human mesenchymal stem cells (HMSCs) and BMPs in therapeutic perspectives and bone tissue engineering. BMPs are potent inducers of osteoblastic differentiation. They exert their actions via BMP receptors (BMPR), including BMPR1A, BMPR1B and BMPR2. Fibroblast growth factor 2 (FGF2) is expressed by cells of the osteoblastic lineage, increases their proliferation and is secreted during the healing process of fractures or in surgery bone sites. We hypothesized that FGF2 might influence HMSC osteoblastic differentiation by modulating expressions of BMPs and their receptors. BMP2, BMP4, BMPR1A and mainly BMPR1B expressions were up-regulated during this differentiation. FGF2 inhibited HMSCs osteoblastic differentiation and the up-regulation of BMPs and BMPR. This effect was prevented by inhibiting the ERK or JNK mitogen-activated protein kinases which are known to be activated by FGF2. These data provide a mechanism explaining the inhibitory effect of FGF2 on osteoblastic differentiation of HMSCs. These crosstalks between growth and osteogenic factors should be considered in the use of recombinant BMPs in therapeutic purpose of fracture repair or skeletal bioengineering.},
doi = {10.1016/J.BBRC.2012.09.129},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 427,
place = {United States},
year = {2012},
month = {11}
}