Meteorin-Like Shows Unique Expression Pattern in Bone and Its Overexpression Inhibits Osteoblast Differentiation.

Meteorin-Like Shows Unique Expression Pattern in Bone and Its Overexpression Inhibits Osteoblast Differentiation.
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DOI:
10.1371/journal.pone.0164446
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Lin S
Lin S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Gong W;Liu Y;Wu Z;Wang S;Qiu G;Lin S

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本研究旨在鉴定和表征成骨细胞功能相关基因。首先,我们构建了人成骨细胞全长cDNA文库,并进行了测序,以筛选功能尚未报道的基因,并通过双荧光素酶报告系统检测这些候选基因与激活蛋白-1(AP-1)转录因子复合物的关系,进一步鉴定这些候选基因。只有一个基因,即METRNL(Meteorin,神经胶质细胞分化调节因子样)已被筛选出来。我们通过免疫组织化学方法分析了METRNL在骨中的表达模式,并建立了稳定转染METRNL-EGFP融合蛋白过表达的MG 63细胞系,以分析METRNL在矿化结节形成中的功能。免疫组化显示METRNL表达于骨小梁表面的肥大软骨细胞和成骨细胞。METRNL过表达抑制MG 63骨肉瘤细胞系矿化结节的形成。因此,所鉴定的与AP-1转录因子复合物活性相关的基因METRNL在骨中具有独特的表达模式。此外,METRNL的异常表达可能抑制骨细胞分化。
The present study was performed to identify and characterize genes involved in osteoblasts function. Firstly, we constructed and sequenced a human osteoblast full-length cDNA library to screen for genes whose functions have not been reported and further identify these candidate genes through detecting the relationship with the activator protein-1 (AP-1) transcription factor complex using a dual luciferase reporter system. Only one gene, namely METRNL (Meteorin, glial cell differentiation regulator-like) has been screened out. We performed immunohistochemistry to analyze expression patterns in bone and established a stable transfection MG63 cell line of METRNL-EGFP fusion protein overexpression to analyze the function of METRNL in mineralized nodule formation. Immunohistochemistry showed METRNL expression in hypertrophic chondrocytes and osteoblasts lining trabecular bone surfaces. Overexpression of METRNL inhibited mineralized nodule formation by the MG63 osteosarcoma cell line. Thus, the identified gene, METRNL, which is associated with AP-1 transcription factor complex activity, has a unique expression pattern in bone. In addition, the anomalous expression of METRNL may inhibit bone cell differentiation.
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