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

• Main Authors: Hughes-Fulford Millie, Li Chai-Fei
• Format: Article
• Language: English
• Published: BMC 2011-02-01
• Series: Journal of Orthopaedic Surgery and Research
• Online Access: http://www.josr-online.com/content/6/1/8

<p>Abstract</p> <p>Introduction</p> <p>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.</p> <p>Materials and methods</p> <p>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.</p> <p>Results</p> <p>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 (<it>egr-1), fgf-2, cyclo-oxygenase-2 (cox-2), tgfβ and </it>matrix metalloproteinase-3 <it>(mmp-3) </it>associated with proliferation and expression of angiogenic genes like vascular endothelial growth factor A (<it>vegfA) </it>and its receptor <it>vegfr1</it>. We found that FGF-2 significantly reduced gene expression associated with mineralization, e.g. <it>collagen type-1 (col1a1), fibronectin (fn), osteocalcin (oc), IGF-1, noggin, bone morphogenic protein (bmp-2) and alkaline phosphatase (alp)</it>. In contrast, BMP-2 significantly stimulated expression of the mineralization associated genes but had little or no effect on gene expression associated with growth.</p> <p>Conclusions</p> <p>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.</p>