Promotion of the intrinsic damage-repair response in articular cartilage by fibroblastic growth factor-2

Promotion of the intrinsic damage-repair response in articular cartilage by fibroblastic growth factor-2
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DOI:
10.1016/j.joca.2005.02.007
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发表时间:
2005-06-01
影响因子:
7
通讯作者:
Davies, ME
Davies, ME
中科院分区:
医学2区
文献类型:
--
作者:
Henson, FMD;Bowe, EA;Davies, ME

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目的:确定成纤维细胞生长因子-2(FGF-2)对体外关节软骨内在损伤修复反应的影响。方法:马类关节软骨外植体,不含软骨下骨,从 2.5 cm 高度施加 500 g 的单次冲击载荷。然后将外植体在0、12、25、50或100ng/ml FGF-2中培养长达28天。未受影响的圆盘作为每个时间点的对照。使用组织学和免疫组织化学技术来量化和表征假定的软骨细胞祖细胞 (CPC) 对损伤和 FGF-2 治疗的反应。结果:FGF-2 显着加速了软骨表面组织学上鉴定的从头修复细胞的出现并增加了其数量。该反应受 FGF-2 剂量的影响。通过表达 II、IX/XI 型胶原蛋白而非 I 型胶原蛋白,修复细胞被证明是软骨细胞。此外,这些细胞以及关节表面下的细胞显示出 Notch-1 和 PCNA(软骨祖细胞增殖标记物)免疫阳性。 结论:本研究的结果表明,在单次冲击负荷后,可以在体外刺激成熟关节软骨中的 CPC。这些 CPC 和由它们产生的细胞似乎代表了软骨对损伤的反应。 FGF-2 可以显着增加 CPC 出现的时间及其总数,这为 FGF-2 在调节软骨修复中的重要作用提供了进一步的证据。这些结果表明,使用这种体外模型进一步研究成熟软骨的修复机制对于了解成熟软骨的修复能力至关重要。 (C) 2005 年国际骨关节炎研究协会。由爱思唯尔有限公司出版。保留所有权利。
Objective: To identify the effect of fibroblastic growth factor-2 (FGF-2) on the intrinsic damage-repair response in articular cartilage in vitro.Methods: Articular equine cartilage explants, without subchondral bone, had a single impact load of 500 g applied from a height of 2.5 cm. Explants were then cultured in 0, 12, 25, 50 or 100 ng/ml FGF-2 for up to 28 days. Unimpacted discs served as controls for each time-point. Histological and immunohistochemical techniques were used to quantify and characterise the response of putative chondrocyte progenitor cells (CPC) to damage and FGF-2 treatment.Results: FGF-2 significantly accelerated the appearance and increased the numbers of de novo repair cells identified histologically at the cartilage surface. The response was affected by the dose of FGF-2. The repair cells were shown to be chondrocytes by their expression of collagen types II, IX/XI, but not of type I collagen. In addition, these cells, and those underlying the articular surface, were shown to be immunopositive for Notch-1 and PCNA, markers for proliferating cartilage progenitor cells.Conclusions: The results of this study indicate that, following single impact load, CPC can be stimulated in mature articular cartilage in vitro. These CPC and the cells arising from them appear to represent the cartilage's response to damage. The timing of the appearance of CPC and their overall numbers can be significantly increased by FGF-2, providing further evidence for an important role for FGF-2 in modulating cartilage repair. These results indicate that further study into the mechanisms of repair in mature cartilage using this in vitro model are vital in understanding the repair capacity of mature cartilage. (C) 2005 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.