Fibroblast growth factor 18 increases the trophic effects of bone marrow mesenchymal stem cells on chondrocytes isolated from late stage osteoarthritic patients.

Fibroblast growth factor 18 increases the trophic effects of bone marrow mesenchymal stem cells on chondrocytes isolated from late stage osteoarthritic patients.
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DOI:
10.1155/2014/125683
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发表时间:
2014
影响因子:
4.3
通讯作者:
Wu J
Wu J
中科院分区:
医学3区
文献类型:
--
作者:
Zhang Z;Wang Y;Li M;Li J;Wu J

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间充质干细胞与软骨细胞共培养增加软骨基质的产生。从晚期骨关节炎患者分离的软骨细胞通常失去其产生软骨基质的表型。成纤维细胞生长因子18被认为使OA软骨细胞再分化为功能活性软骨细胞。本研究的目的是探讨骨髓间充质干细胞对骨关节炎软骨细胞的支持作用,并测试在共培养系统中,FGF18是否可以增强骨关节炎软骨细胞对骨髓间充质干细胞支持的反应性。使用沉淀和transwell共培养物。进行GAG定量、羟脯氨酸测定和qPCR。还应用了软骨形成的异位模型。我们的数据表明,在骨髓间充质干细胞和骨关节炎软骨细胞的颗粒共培养中,与软骨细胞的单一培养相比,在FGF18的存在下基质产生增加。transwell共培养结果显示,在培养液中加入FGF18的MSCs与OA软骨细胞共培养后,OA软骨细胞基质生成基因的表达增加,而肥大基因的表达无明显变化。最后,骨髓间充质干细胞与骨关节炎软骨细胞共植入产生更多的基质比软骨细胞。总之,FGF18可以恢复OA软骨细胞对MSC营养作用的反应性。骨髓间充质干细胞与经FGF 18处理的骨关节炎软骨细胞共植入可能是骨关节炎病理变化过程中降解的软骨组织再生的良好替代细胞来源。
Coculture of mesenchymal stem cells with chondrocytes increases production of cartilaginous matrix. Chondrocytes isolated from late stage osteoarthritic patients usually lost their phenotype of producing cartilaginous matrix. Fibroblast growth factor 18 is believed to redifferentiate OA chondrocyte into functionally active chondrocytes. The aim of this study is to investigate the supportive effects of MSCs on OA chondrocytes and test if FGF18 could enhance the responsiveness of OA chondrocytes to the support of MSCs in a coculture system. Both pellet and transwell co-cultures were used. GAG quantification, hydroxyproline assay, and qPCR were performed. An ectopic models of cartilage formation was also applied. Our data indicated that, in pellets coculture of MSCs and OA chondrocytes, matrix production was increased in the presence of FGF18, comparing to the monoculture of chondrocytes. Results from transwell coculture study showed that expression of matrix producing genes in OA chondrocytes increased when cocultured with MSCs with FGF18 in culture medium, while hypertrophic genes were not changed by coculture. Finally, coimplantation of MSCs with OA chondrocytes produces more matrix than chondrocytes only. In conclusion, FGF18 can restore the responsiveness of OA chondrocytes to the trophic effects of MSCs. Coimplantation of MSCs and OA chondrocytes treated with FGF18 may be a good alternative cell source for regenerating cartilage tissue that is degraded during OA pathological changes.
与关节软骨细胞和间充质干细胞共培养的软骨发生增强。
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