基因表达分析表明，与骨骼发育相关的基因GDF5和DIO2参与儿童而非成人大骨节病的发展。
Gene expression analysis suggests bone development-related genes GDF5 and DIO2 are involved in the development of Kashin-Beck disease in children rather than adults.
作者信息
Wen Yan, Zhang Feng, Li Chunyan, He Shulan, Tan Wuhong, Lei Yanxia, Zhang Qiang, Yu Hanjie, Zheng Jingjing, Guo Xiong
机构信息
School of Public Health, Health Science Center, Key Laboratory of Environment and Gene Related Diseases of Ministry Education, Key Laboratory of Trace Elements and Endemic Diseases of Ministry Health, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
Department of Kashin-Beck Diseases, Qinghai Institute for Endemic Disease Control and Prevention, Xining, Qinghai, P. R. China.
出版信息
PLoS One. 2014 Jul 29;9(7):e103618. doi: 10.1371/journal.pone.0103618. eCollection 2014.
OBJECTIVE
To investigate the differences in gene expression between children and adults with Kashin-Beck disease (KBD).
METHODS
12 children with KBD and 12 healthy children were selected and divided into 4 KBD vs. control pairs matched according to age and gender, with each pair having 3 KBD children and 3 healthy children. Additionally, 15 adults with KBD and 15 healthy adults were selected and divided into 5 KBD vs. control pairs matched according to age and gender, with each pair having 3 KBD adults and 3 healthy adults. Total RNA was isolated from peripheral blood mononuclear cells (PBMCs) respectively. A total of 367 target genes were selected based on previous genome-wide gene expression profile analysis. Expression levels of the 367 genes were evaluated by customized oligonucleotide microarray and the differentially expressed genes were identified. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was conducted to validate the microarray data.
RESULTS
A total of 95 (25.9%) genes in KBD children and 158 (43.1%) genes in KBD adults were found to exhibit more than two-fold change in gene expression level relative to healthy controls. By comparing differentially expressed genes identified in KBD children to those of KBD adults, 42 genes were found to be differentially expressed only in KBD children. And 105 genes were found to be differentially expressed only in KBD adults. Further, 16 differentially expressed genes common to both KBD children and adults were found to be asynchronously expressed in KBD children compared to KBD adults.
CONCLUSION
Significant differences in gene expression pattern were identified between KBD children and KBD adults, indicating different molecular mechanisms underlying cartilage lesions of KBD children and KBD adults. In addition, bone development-related genes GDF5 (expression ratio = 2.14±0.02) and DIO2 (expression ratio = 0.11±0.05) may contribute to the development of KBD in children rather than in adults.
目的
研究大骨节病（KBD）患儿与成人基因表达的差异。
方法
选取12例KBD患儿和12例健康儿童，按年龄和性别分为4对KBD组与对照组，每对中有3例KBD患儿和3例健康儿童。此外，选取15例KBD成人和15例健康成人，按年龄和性别分为5对KBD组与对照组，每对中有3例KBD成人和3例健康成人。分别从外周血单个核细胞（PBMCs）中提取总RNA。基于之前的全基因组基因表达谱分析，共选择367个靶基因。通过定制的寡核苷酸微阵列评估这367个基因的表达水平，并鉴定差异表达基因。进行定量实时逆转录聚合酶链反应（qRT-PCR）以验证微阵列数据。
结果
相对于健康对照，发现KBD患儿中有95个（25.9%）基因、KBD成人中有158个（43.1%）基因的表达水平变化超过两倍。通过比较KBD患儿与KBD成人中鉴定出的差异表达基因，发现42个基因仅在KBD患儿中差异表达。并且发现105个基因仅在KBD成人中差异表达。此外，发现KBD患儿和成人共有的16个差异表达基因在KBD患儿中的表达与KBD成人不同步。
结论
KBD患儿与KBD成人的基因表达模式存在显著差异，表明KBD患儿和KBD成人软骨损伤背后的分子机制不同。此外，骨发育相关基因GDF5（表达比值=2.14±0.02）和DIO2（表达比值=0.11±0.05）可能在儿童而非成人KBD的发生发展中起作用。
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