The role of FGF-2 and BMP-2 in regulation of gene induction, cell proliferation and mineralization.

dc.contributor.authorHughes-Fulford, Millieen
dc.contributor.authorLi, Chai-Feien
dc.date.accessioned2012-08-24T11:12:57Zen
dc.date.available2012-08-24T11:12:57Zen
dc.date.issued2011-02-09en
dc.date.updated2012-08-24T11:12:57Zen
dc.description.abstractIntroduction The difficulty in re-growing and mineralizing new bone after severe fracture can result in loss of ambulation or limb. Here we describe the sequential roles of FGF-2 in inducing gene expression, cell growth and BMP-2 in gene expression and mineralization of bone. Materials and methods The regulation of gene expression was determined using real-time RTPCR (qRTPCR) and cell proliferation was measured by thymidine incorporation or fluorescent analysis of DNA content in MC3T3E1 osteoblast-like cells. Photomicroscopy was used to identify newly mineralized tissue and fluorescence was used to quantify mineralization. Results Fibroblast growth factor-2 (FGF-2) had the greatest ability to induce proliferation after 24 hours of treatment when compared to transforming growth factor beta (TGFβ, insulin-like growth factor-1 (IGF-1), bone morphogenic protein (BMP-2), platelet derived growth factor (PDGF) or prostaglandin E2 (PGE2). We found that FGF-2 caused the most significant induction of expression of early growth response-1 (egr-1), fgf-2, cyclo-oxygenase-2 (cox-2), tgfβ and matrix metalloproteinase-3 (mmp-3) associated with proliferation and expression of angiogenic genes like vascular endothelial growth factor A (vegfA) and its receptor vegfr1. We found that FGF-2 significantly reduced gene expression associated with mineralization, e.g. collagen type-1 (col1a1), fibronectin (fn), osteocalcin (oc), IGF-1, noggin, bone morphogenic protein (bmp-2) and alkaline phosphatase (alp). In contrast, BMP-2 significantly stimulated expression of the mineralization associated genes but had little or no effect on gene expression associated with growth. Conclusions The ability of FGF-2 to re-program a mineralizing gene expression profile to one of proliferation suggests that FGF-2 plays a critical role of osteoblast growth in early fracture repair while BMP-2 is instrumental in stimulating mineralization.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationJournal of Orthopaedic Surgery and Research. 2011 Feb 09;6(1):8en
dc.identifier.doihttps://doi.org/10.1186/1749-799X-6-8en
dc.identifier.urihttp://hdl.handle.net/10919/18816en
dc.language.isoenen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.holderMillie Hughes-Fulford et al.; licensee BioMed Central Ltd.en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleThe role of FGF-2 and BMP-2 in regulation of gene induction, cell proliferation and mineralization.en
dc.title.serialJournal of Orthopaedic Surgery and Researchen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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