title: Fibroblast growth factor 2 inhibits up-regulation of bone morphogenic proteins and their receptors during osteoblastic differentiation of human mesenchymal stem cells.
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.
authors.affiliation: Physiopathology of Inflammatory Bone Diseases, EA 4490, University Lille North of France, Quai Masset, Bassin Napoléon, BP120, 62327 Boulogne sur Mer, France. ebiver@yahoo.fr
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Biver
authors.forename: Anne-Sophie
authors.initials: AS
authors.lastname: Soubrier
authors.forename: Cyril
authors.initials: C
authors.lastname: Thouverey
authors.forename: Bernard
authors.initials: B
authors.lastname: Cortet
authors.forename: Odile
authors.initials: O
authors.lastname: Broux
authors.forename: Joseph
authors.initials: J
authors.lastname: Caverzasio
authors.forename: Pierre
authors.initials: P
authors.lastname: Hardouin
mesh_terms: D052004:Bone Morphogenetic Protein Receptors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D019485:Bone Morphogenetic Proteins; D016222:Fibroblast Growth Factor 2; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D052004:Bone Morphogenetic Protein Receptors