Authors: R A Power U T Iwaniec K A Magee N G MitovaCaneva T J Wronski
Publish Date: 2004/03/30
Volume: 15, Issue: 9, Pages: 716-723
Abstract
Basic fibroblast growth factor bFGF has a strong bone anabolic effect in intact and ovariectomized OVX rats treated for 7–14 days Other growth factors such as IGFI and TGFβ have been implicated as potential mediators for this effect The purpose of this study was to examine the early effects of bFGF therapy in vivo on bone formation and gene expression in OVX rats in order to determine whether upregulation of gene expression for IGFI and/or TGFβ precedes or coincides with the stimulatory effects of bFGF on bone formation At 3 months of age Sprague Dawley rats were OVX or shamoperated SHAM then maintained untreated for 3 months One group of baseline OVX rats BSL OVX and BSL SHAM rats were then killed Additional OVX groups were treated IV with bFGF at a daily dose of 200 μg/kg and killed at 1–7 and 10 days Another group of OVX rats was treated IV with vehicle daily for 10 days then killed Lumbar vertebrae were processed for cancellous bone histomorphometry or RNA isolation Ovariectomy induced increased cancellous bone turnover and a significant decrease in vertebral bone mass Treatment of OVX rats with bFGF resulted in a significant increase in bone formation As early as 24 h after bFGF treatment of OVX rats osteoblast surface osteoid surface and osteoid volume were more than double those in BSL OVX rats and continued to increase with time These variables were also significantly higher in bFGFtreated OVX rats at 10 days compared with vehicletreated OVX rats Gene expression for IGFI was not different between BSL OVX rats and bFGFtreated OVX rats at 1 day but was significantly higher by approximately 50 in OVX rats treated with bFGF for 2 and 7 days and was also significantly higher by nearly 75 in OVX rats treated for 10 days compared with OVX rats treated with vehicle Gene expression for TGFβ1 was unchanged at early times and only significantly upregulated by a relatively modest 30 in OVX rats treated with bFGF for 10 days The results indicate that the bone anabolic effects of bFGF in OVX rats begin as early as 24 h following the initial treatment and increase with time These early stages of the strong stimulatory effect of bFGF on bone formation were not associated with a large upregulation of gene expression for IGFI and TGFβ The rapid increase in osteoblast surface in bFGFtreated OVX rats suggests that the growth factor induces conversion of bone lining cells to osteoblastsBasic FGF was obtained through the generosity of Dr Judy Abraham of Chiron Corp Emeryville Calif USA The authors are grateful to Dr Russell Turner and Ms Minzhi Zhang of the Mayo Clinic Rochester Minn USA for probes used in molecular assays and technical advice The authors would also like to thank Ms Friba Faqueeri for assistance in RNA isolation This research was supported by National Institutes of Health grant R37 AG09241 from the National Institute on Aging
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