Systemic administration of acidic fibroblast growth factor (FGF-1) prevents bone loss and increases new bone formation in ovariectomized rats
Systemic administration of acidic fibroblast growth factor (FGF-1) prevents bone loss and increases new bone formation in ovariectomized rats
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DOI：
10.1359/jbmr.1999.14.6.953
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发表时间：
1999-06-01
影响因子：
6.2
通讯作者：
Mundy, GR
中科院分区：
文献类型：
--
作者：
Dunstan, CR;Boyce, R;Mundy, GR
目前还没有普遍接受的药物可以显著增加骨质疏松症患者的骨量。许多在正常骨形成中起重要作用的多肽，如转化生长因子-β超家族的成员，对于这一目的并不令人满意，要么是因为它们的有益作用主要是局部的，要么是因为它们的使用存在全身毒性。我们研究了外源性成纤维细胞生长因子-1和-2(FGF1和FGF2)在体内对骨的影响。由于FGFs是骨骼正常发育所必需的，所以在假手术或卵巢切除(OVX)后即刻和6个月后，成年雌性大鼠尾静脉注射FGF1(0.2 mg/kg)，连续28天。在OVX后立即处理的大鼠，OVX导致胫骨骨密度下降30%以上，这可被FGF1和雌激素阻止，但FGF1也具有合成代谢作用。在假手术大鼠，成纤维细胞生长因子-1使骨密度增加2倍，而雌激素没有作用。在去卵巢后6个月的大鼠中，严重的骨丢失和骨小梁微结构的破坏与严重的骨质疏松症患者相似。在这些大鼠中，应用成纤维细胞生长因子-1诱导了广泛的新编织骨形成，新的骨小梁样结构填充了大部分骨髓间隙，胫骨干骺端的骨密度增加了3倍。在小鼠的头盖骨皮下注射成纤维细胞生长因子-1和成纤维细胞生长因子-2，剂量为2-2000微克/天，连续3天，对其进行形态学检查，结果显示骨形成显著增加。因此，我们得出结论，局部和全身的成纤维细胞生长因子-1都增加了新骨形成和骨密度，全身成纤维细胞生长因子-1似乎也恢复了骨的微结构，并防止了与雌激素停用相关的骨丢失。
There are no universally accepted agents that will substantially increase bone mass in osteoporotic patients. A number of peptides important in normal bone formation, such as members of the transforming growth factor-beta superfamily, are not satisfactory for this purpose either because their beneficial effects are predominantly local or there is systemic toxicity associated with their administration. We have examined the effects of exogenous fibroblast growth factor-1 and -2 (FGF-1 and FGF-2) on bone in vivo, since FGFs have been shown recently to be essential for normal skeletal development, FGF-1 was injected daily (0.2 mg/kg intravenously) for 28 days into the tail vein of adult female rats immediately following and 6 months after sham operation or ovariectomy (OVX), In rats treated immediately post-OVX, OVX produced more than a 30% decrease in tibial bone density, which was prevented by FGF-1 and estrogen, However, FGF-1 also had an anabolic effect. In sham-operated rats, FGF-1 increased bone density to 2-fold, whereas estrogen had no effect. In rats 6 months post-OVX, severe bone loss and disruption of trabecular microarchitecture occurred similar to that seen in patients with severe osteoporosis. In these rats, administration of FGF-1 induced extensive new woven bone formation with new trabecular-like structures filling much of the marrow spaces, and bone density in the tibial metaphysis increased 3-fold. FGF-1 and FGF-2 were also administered subcutaneously over the calvaria of mice in doses of 2-2000 mu g/day for 3 days and shown to produce substantial increases in bone formation when examined morphologically. Thus, we conclude that both local and systemic FGF-1 increases new bone formation and bone density, and systemic FGF-1 also appears to restore bone microarchitecture and prevent bone loss associated with estrogen-withdrawal.