PMID- 21306641
OWN - NLM
STAT- MEDLINE
DCOM- 20120301
LR  - 20211020
IS  - 1749-799X (Electronic)
IS  - 1749-799X (Linking)
VI  - 6
DP  - 2011 Feb 9
TI  - The role of FGF-2 and BMP-2 in regulation of gene induction, cell proliferation 
      and mineralization.
PG  - 8
LID - 10.1186/1749-799X-6-8 [doi]
AB  - INTRODUCTION: 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 (TGFbeta, insulin-like growth factor-1 (IGF-1), bone 
      morphogenic protein (BMP-2), platelet derived growth factor (PDGF) or 
      prostaglandin E(2) (PGE(2)). 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), tgfbeta 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.
FAU - Hughes-Fulford, Millie
AU  - Hughes-Fulford M
AD  - Department of Research, Veterans Affairs Medical Center, 4150 Clement Street, San 
      Francisco, CA 94121, USA. millie.hughes-fulford@ucsf.edu
FAU - Li, Chai-Fei
AU  - Li CF
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20110209
PL  - England
TA  - J Orthop Surg Res
JT  - Journal of orthopaedic surgery and research
JID - 101265112
RN  - 0 (Bmp2 protein, mouse)
RN  - 0 (Bone Morphogenetic Protein 2)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Transforming Growth Factor beta)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Animals
MH  - Bone Morphogenetic Protein 2/genetics/pharmacology/*physiology
MH  - Calcification, Physiologic/drug effects/*physiology
MH  - Cell Differentiation/drug effects/physiology
MH  - Cell Line
MH  - *Cell Proliferation/drug effects
MH  - Dinoprostone/pharmacology
MH  - Fibroblast Growth Factor 2/genetics/pharmacology/*physiology
MH  - Gene Expression Regulation/drug effects/*physiology
MH  - In Vitro Techniques
MH  - Insulin-Like Growth Factor I/pharmacology
MH  - Mice
MH  - Osteoblasts/*cytology/drug effects/*physiology
MH  - Platelet-Derived Growth Factor/pharmacology
MH  - Time Factors
MH  - Transforming Growth Factor beta/pharmacology
PMC - PMC3044105
EDAT- 2011/02/11 06:00
MHDA- 2012/03/02 06:00
PMCR- 2011/02/09
CRDT- 2011/02/11 06:00
PHST- 2010/07/29 00:00 [received]
PHST- 2011/02/09 00:00 [accepted]
PHST- 2011/02/11 06:00 [entrez]
PHST- 2011/02/11 06:00 [pubmed]
PHST- 2012/03/02 06:00 [medline]
PHST- 2011/02/09 00:00 [pmc-release]
AID - 1749-799X-6-8 [pii]
AID - 10.1186/1749-799X-6-8 [doi]
PST - epublish
SO  - J Orthop Surg Res. 2011 Feb 9;6:8. doi: 10.1186/1749-799X-6-8.