Effects of single and cyclical local injections of basic fibroblast growth factor on cancellous bone defects in rabbits

Effects of single and cyclical local injections of basic fibroblast growth factor on cancellous bone defects in rabbits
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DOI:
10.1007/s00776-009-1403-2
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发表时间:
2009-11-01
影响因子:
1.7
通讯作者:
Shimada, Yoichi
Shimada, Yoichi
中科院分区:
医学4区
文献类型:
--
作者:
Kamo, Keiji;Miyakoshi, Naohisa;Shimada, Yoichi

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局部应用碱性成纤维细胞生长因子(bFGF)对骨形成具有合成代谢作用。由于其半衰期短,需要用于局部治疗的递送系统来提高功效。然而,很少有人知道周期性局部注射bFGF的影响。我们评价了在兔股骨髁部松质骨缺损处单次和周期性局部注射bFGF的效果,以“仅赋形剂”作为对照,将单次低剂量(40 μ g)、单次高剂量(120 μ g)或周期性低剂量(40 μ g,3次)bFGF持续注射到植入明胶海绵的骨缺损中。术后4周处死兔,取股骨进行评价,与对照组相比,bFGF单次和周期性给药均能剂量依赖性地增加骨缺损处的新骨形成量(P < 0.01)和骨密度(P < 0.01)。然而,仅高剂量bFGF注射组骨缺损处松质骨体积显著增加(P < 0.05),与对照组相比,使用骨组织形态计量学。与单次低剂量和高剂量bFGF给药相比,周期性注射bFGF显著增加了runt相关转录因子2(Runx 2)阳性细胞的数量(分别为P < 0.01和P < 0.05),与对照组相比,单次高剂量和周期性给药显著增加了骨桥蛋白阳性细胞的数量结果提示,在松质骨愈合早期大剂量注射bFGF能更有效地增加松质骨体积,周期性注射bFGF可能对骨祖细胞有刺激作用。
Local administration of basic fibroblast growth factor (bFGF) has anabolic effects on bone formation. A delivery system for local treatment is required to increase efficacy because of its short half-life. However, little is known about the effects of cyclical local injection of bFGF. We evaluated the effects of single and cyclical local injection of bFGF at a cancellous bone defect in the femoral condyle in rabbits.Using the "vehicle only" as a control, a single low dose (40 A mu g), single high dose (120 A mu g), or cyclical low dose (40 A mu g, three times) of bFGF was injected percutaneously into a bone defect implanted with a gelatin sponge. The rabbits were killed at 4 weeks after surgery and the femurs were harvested for evaluation.Both single and cyclical administration of bFGF dose-dependently increased the amount of new bone formation in the bone defect using radiographs (P < 0.01) and bone mineral density (BMD) measurements (P < 0.01) compared to controls. However, only high-dose bFGF injection significantly increased the cancellous bone volume at the bone defect (P < 0.05) compared to controls, using bone histomorphometry. Cyclical injection of bFGF significantly increased the number of runt-related transcription factor-2 (Runx2)-positive cells compared to single low- and high-dose bFGF administration (P < 0.01 and P < 0.05, respectively), and single high-dose and cyclical administration significantly increased the number of osteopontin-positive cells compared to controls (P < 0.01), based on immunohistochemical analysis.These results suggest that high-dose injection of bFGF, at the very early stage of cancellous bone healing, is more effective in increasing cancellous bone volume, and cyclical injection of bFGF may stimulate osteoprogenitor cells.