A genome-wide analysis of the gene expression profiles and alternative splicing events during the hypoxia-regulated osteogenic differentiation of human cartilage endplate-derived stem cells.
A genome-wide analysis of the gene expression profiles and alternative splicing events during the hypoxia-regulated osteogenic differentiation of human cartilage endplate-derived stem cells.
复制标题
对人软骨终板干细胞缺氧调节成骨分化过程中基因表达谱和选择性剪接事件的全基因组分析
DOI：
10.3892/mmr.2017.6846
复制
发表时间：
2017-08
影响因子：
3.4
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Yao Y;Deng Q;Sun C;Song W;Liu H;Zhou Y
据推测，椎间盘退变是由软骨终板（CEP）退变引发的，其特征是软骨骨化。 CEP 衍生的干细胞 (CESC) 具有软骨成骨分化的潜力，可能负责 CEP 中软骨化和骨化之间的平衡。 CEP 仍处于无血管和缺氧的微环境中；本研究观察到缺氧能够显着抑制CESCs的成骨分化。这种响应缺氧微环境的组织特异性 CESC 分化对于预防 CEP 中的骨化具有重要的生理意义。为了研究CESCs成骨分化的缺氧调控机制，采用Human Transcriptome Array 2.0检测缺氧条件下CESCs成骨分化过程中的差异表达基因（DEG）和可变剪接基因（ASG），并与常氧条件下诱导的成骨分化过程进行比较。 DEGs和ASGs的高通量分析表明，补体途径中的基因富集，这可能是缺氧抑制CESCs成骨的潜在机制。本研究的结果可能为未来关于缺氧调节的成骨抑制过程中基因表达水平和选择性剪接事件的机制研究提供基础，这可能有助于确定 CEP 变性治疗的靶点。
It has been hypothesized that intervertebral disc degeneration is initiated by degeneration of the cartilage endplate (CEP), which is characterized by cartilage ossification. CEP-derived stem cells (CESCs), with the potential for chondro-osteogenic differentiation, may be responsible for the balance between chondrification and ossification in the CEP. The CEP remains in an avascular and hypoxic microenvironment; the present study observed that hypoxia was able to markedly inhibit the osteogenic differentiation of CESCs. This tissue-specific CESC differentiation in response to a hypoxic microenvironment was physiologically important for the prevention of ossification in the CEP. In order to study the hypoxia-regulated mechanisms underlying osteogenic differentiation of CESCs, a Human Transcriptome Array 2.0 was used to detect differentially expressed genes (DEGs) and alternatively spliced genes (ASGs) during the osteogenic differentiation of CESCs under hypoxia, compared with those induced under normoxia. High-throughput analysis of DEGs and ASGs demonstrated that genes in the complement pathway were enriched, which may be a potential mechanism underlying hypoxia inhibition of CESCs osteogenesis. The results of the present study may provide a basis for future mechanistic studies regarding gene expression levels and alternative splicing events during the hypoxia-regulated inhibition of osteogenesis, which may be helpful in identifying targets for CEP degeneration therapy.
登录
查看更多内容
影响因子：
6.2
作者：
Duque, Gustavo;Huang, Dao Chao;Kremer, Richard
通讯作者：
Kremer, Richard
影响因子：
5.2
作者：
Duque, Gustavo;Huang, Dao Chao;Kremer, Richard
通讯作者：
Kremer, Richard
影响因子：
3
作者：
BUCKWALTER, JA
通讯作者：
BUCKWALTER, JA
影响因子：
2.8
作者：
Babadagli, Mustafa Ege;Tezcan, Berna;Tufan, A. Cevik
通讯作者：
Tufan, A. Cevik
Osf2/Cbfa1：成骨细胞分化的转录激活因子
影响因子：
64.5
作者：
Ducy, P;Zhang, R;Karsenty, G
通讯作者：
Karsenty, G