Charles Lyndon F, Woodman Jessica L, Ueno Daisuke, Gronowicz Gloria, Hurley Marja M, Kuhn Liisa T
Department of Reconstructive Sciences, University of Connecticut Health Center, Farmington, CT 06030, USA.
Unit of Oral and Maxillofacial Implantology, Tsurumi University School of Dental Medicine, Yokohama, Japan.
Exp Gerontol. 2015 Apr;64:62-9. doi: 10.1016/j.exger.2015.02.006. Epub 2015 Feb 12.
There is an age-associated reduction in the bone healing activity of bone morphogenetic protein-2 (BMP-2) that is currently addressed by administering higher doses of BMP-2 in elderly patients. The unwanted medical complications from high dose BMP-2 motivated this investigation to determine whether the addition of a low dose of fibroblast growth factor 2 (FGF-2) could enhance the ability of a lower dose of BMP-2 to heal calvarial bone defects in old mice (18-20 months old). FGF-2 (5 ng) and BMP-2 (2 μg) were administered by a controlled release two-phase biomaterial scaffold placed into the bone defect. FGF-2 released more rapidly and completely in vitro than BMP-2 (40% vs 2%). In vivo, both BMP-2 and FGF-2+BMP-2 groups formed more new bone in calvarial defects than scaffold alone (p < 0.001) or FGF-2 only groups (p < 0.01). The overall total volume of new bone was not statistically increased by the addition of FGF-2 to BMP-2 as measured by microCT, but the pattern of bone deposition was different. In old mice, but not young, there was enhanced bony fill in the central bone defect area when the BMP-2 was supplemented with FGF-2. Histological analysis of the center of the defect revealed an increased bone volume (%BV/TV (p = 0.004)) from the addition of FGF-2. These studies suggest that combining a low dose of FGF-2 with a low dose of BMP-2 has the potential to increase bone healing in old mice relative to BMP-2 alone.
骨形态发生蛋白-2(BMP-2)的骨愈合活性会随着年龄增长而降低,目前老年患者通过施用更高剂量的BMP-2来解决这一问题。高剂量BMP-2带来的不良医学并发症促使本研究确定添加低剂量的成纤维细胞生长因子2(FGF-2)是否能增强低剂量BMP-2修复老年小鼠(18 - 20月龄)颅骨缺损的能力。通过置于骨缺损处的控释两相生物材料支架施用FGF-2(5纳克)和BMP-2(2微克)。FGF-2在体外比BMP-2释放得更快且更完全(40%对2%)。在体内,BMP-2组和FGF-2 + BMP-2组在颅骨缺损处形成的新骨都比单独使用支架组(p < 0.001)或仅使用FGF-2组(p < 0.01)更多。通过显微CT测量,添加FGF-2到BMP-2后新骨的总体积没有统计学上的增加,但骨沉积模式不同。在老年小鼠而非年轻小鼠中,当BMP-2补充FGF-2时,中央骨缺损区域的骨填充增强。对缺损中心的组织学分析显示,添加FGF-2后骨体积增加(%BV/TV(p = 0.004))。这些研究表明,相对于单独使用BMP-2,低剂量FGF-2与低剂量BMP-2联合使用有增加老年小鼠骨愈合的潜力。