Age-Related Changes in FGF-2, Fibroblast Growth Factor Receptors and β-Catenin Expression in Human Mesenchyme-Derived Progenitor Cells.
Age-Related Changes in FGF-2, Fibroblast Growth Factor Receptors and β-Catenin Expression in Human Mesenchyme-Derived Progenitor Cells.
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DOI：
10.1002/jcb.25357
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发表时间：
2016-03
影响因子：
4
通讯作者：
Xiao L
中科院分区：
文献类型：
--
作者：
Hurley MM;Gronowicz G;Zhu L;Kuhn LT;Rodner C;Xiao L
FGF-2刺激前成骨细胞复制，敲除小鼠中的Fgf 2基因导致随年龄增长的骨质减少，这与Wnt-β-连环蛋白信号传导减少有关。此外，成骨细胞祖细胞中FGF-2的靶向表达通过Wnt-β-连环蛋白信号传导增加小鼠的骨量。我们推测，人间充质来源的祖细胞（HMDPCs）的内在增殖能力随着年龄的增长而减少，部分原因是FGF-2的减少。为了验证这一假设，从年轻（27~38岁）、中年（47~56岁）和老年（65~76岁）女性受试者的骨中分离HMDPC。HMDPCs培养物大多是同质的，其中大于90%的间充质祖细胞，通过荧光激活细胞分选确定。HMDPCs中FGF 2和FGFR 1 mRNA和蛋白表达随年龄增长而逐渐降低。由于FGF-2激活β-catenin，这可以增强骨形成，我们还评估了其在HMDPC中的年龄相关表达。总β-Catenin mRNA和蛋白表达量随年龄增加而降低。然而，老年HMDSC中β-连环蛋白水平增加，活化β-连环蛋白水平降低。FGF-2处理增加了老年HMDPC中FGFR 1和β-Catenin蛋白，降低了β-Catenin水平，并增加了活化的β-Catenin。总之，Fgf 2表达的减少可能通过调节Wnt-β-catenin信号通路而导致HMDPCs的年龄相关功能受损。
FGF-2 stimulates preosteoblast replication, and knockout of the Fgf2 gene in mice resulted in osteopenia with age, associated with decreased Wnt–β-Catenin signaling. In addition, targeted expression of FGF-2 in osteoblast progenitors increased bone mass in mice via Wnt-β-Catenin signaling. We posited that diminution of the intrinsic proliferative capacity of human mesenchyme-derived progenitor cells (HMDPCs) with age is due in part to reduction in FGF-2. To test this hypothesis HMDPCs from young (27~38), middle aged (47~56) and old (65~76) female human subjects were isolated from bone discarded after orthopedic procedures. HMDPCs cultures were mostly homogeneous with greater than 90% mesenchymal progenitor cells, determined by fluorescence-activated cell sorting. There was a progressive decrease in Fgf2 and FGFR1 mRNA and protein in HMDPCs with age. Since FGF-2 activates β-catenin, which can enhance bone formation, we also assessed its age-related expression in HMDPCs. An age-related decrease in total-β-Catenin mRNA and protein expression was observed. However there were increased levels of p-β-Catenin and decreased levels of activated-β-Catenin in old HMDSCs. FGF-2 treatment increased FGFR1 and β-Catenin protein, reduced the level of p-β-Catenin and increased activated-β-Catenin in aged HMDPCs. In conclusion, reduction in Fgf2 expression could contribute to age-related impaired function of HMDPCs via modulation of Wnt-β-catenin signaling.