Fibroblast growth factor-18 is a trophic factor for mature chondrocytes and their progenitors
Fibroblast growth factor-18 is a trophic factor for mature chondrocytes and their progenitors
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DOI：
10.1053/joca.2002.0514
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发表时间：
2002-04-01
影响因子：
7
通讯作者：
Hughes, SD
中科院分区：
文献类型：
--
作者：
Ellsworth, JL;Berry, J;Hughes, SD
目的：本研究的目的是观察重组人Fgf 18在体内外对软骨细胞增殖和基质生成的影响，并检测成人关节软骨中Fgf 18和Fgf受体（Fgfr）的表达。腺病毒-将FGF 18介导的转移到小鼠耳廓中并将FGF 18添加到成人关节软骨细胞的原代培养物中以评估其作用结果：腺病毒介导的Fgf 18基因转染小鼠关节软骨细胞后，软骨细胞数量明显增加。软骨细胞通过甲苯胺蓝和针对II型胶原的单克隆抗体染色来鉴定。通过原位杂交在这些细胞内检测到Fgf 18、Fgfr 2-（IIIc）、Fgfr 3-（IIIc）和Fgfr 4 mRNA。软骨细胞的细胞核用PCNA和FGF受体（FGFR）2的抗体染色。向原代关节软骨细胞的培养基中添加FGF 18增加了这些细胞的增殖并增加了它们的细胞外基质的产生。为了评估FGF 18的受体选择性，使用稳定表达Fgfr 1-3的主要剪接变体的基因的BaF 3细胞。通过与FGF 18孵育，表达Fgfr 3-（IIIc）或Fgfr 2-（IIIc）的细胞的增殖增加。使用FGFR-Fc融合蛋白和表达Fgfr 3-（IIIc）的BaF 3细胞，仅FGFR 3-（IIIc）-Fc、FGFR 2-（IIIc）-Fc或FGFR 4-Fc降低FGF 18介导的细胞增殖。Fgf 18、Fgfr 3-（IIIc）和Fgfr 2-（IIIc）mRNAs在人关节软骨细胞中的原位杂交结果表明，Fgf 18可作为体内弹性软骨细胞及其祖细胞和体外培养的关节软骨细胞的营养因子。FGF 18及其两种受体基因在软骨细胞中的表达表明FGF 18可能在正常关节软骨的生物学中起自分泌作用。(C)2002年国际骨关节炎研究学会。
Objective: The aim of this study was to examine the effects of recombinant human Fgf18 on chondrocyte proliferation and matrix production in vivo and in vitro, In addition, the expressions of Fgf18 and Fgf receptors (Fgfr) in adult human articular cartilage were examined.Methods: Adenovirus-mediated transfer of Fgf18 into murine pinnae and addition of FGF18 to primary cultures of adult articular chondrocytes were used to assess the effects of FGF18 on chondrocytes, In situ hybridization was used to examine the expression of Fgf18 and Fgfrs in adult human articular cartilage.Results: Expression of Fgf18 by adenovirus-mediated gene transfer in murine pinnae resulted in a significant increase in chondrocyte number. Chondrocytes were identified by staining with toluidine blue and a monoclonal antibody directed against type II collagen. Fgf18, Fgfr 2-(IIIc), Fgfr 3-(IIIc), and Fgfr 4 mRNAs were detected within these cells by in situ hybridization. The nuclei of the chondrocytes stained with antibodies to PCNA and FGF receptor (FGFR) 2. Addition of FGF18 to the culture media of primary articular chondrocytes increased the proliferation of these cells and increased their production of extracellular matrix. To assess the receptor selectivity of FGF18, BaF3 cells stably expressing the genes for the major splice variants of Fgfr 1-3 were used. Proliferation of cells expressing Fgfr 3-(IIIc) or Fgfr 2-(IIIc) was increased by incubation with FGF18. Using FGFR-Fc fusion proteins and BaF3 cells expressing Fgfr 3-(IIIc), only FGFR 3-(IIIc)-Fc, FGFR 2-(IIIc)-Fc or FGFR 4-Fc reduced FGF18-mediated cell proliferation. Expression of Fgf18, Fgfr 3-(IIIc) and Fgfr 2-(IIIc) mRNAs was localized to chondrocytes of human articular cartilage by in situ hybridization.Conclusion: These data demonstrate that Fgf18 can act as a trophic factor for elastic chondrocytes and their progenitors in vivo and articular chondrocytes cultured in vitro. Expression of Fgf18 and the genes for two of its receptors in chondrocytes suggests that Fgf18 may play an autocrine role in the biology of normal articular cartilage. (C) 2002 OsteoArthritis Research Society International.