Comparison of HIF1A-AS1 and HIF1A-AS2 in regulating HIF-1α and the osteogenic differentiation of PDLCs under hypoxia
Comparison of HIF1A-AS1 and HIF1A-AS2 in regulating HIF-1α and the osteogenic differentiation of PDLCs under hypoxia
复制标题
DOI：
10.3892/ijmm.2017.3138
复制
发表时间：
2017-11-01
影响因子：
5.4
通讯作者：
Deng, Jianqing
中科院分区：
文献类型：
--
作者：
Chen, Dongru;Wu, Liping;Deng, Jianqing
低氧诱导因子-1 α（HIF-1 α）是调节牙周膜细胞（PDLCs）成骨分化的关键因子。HIF-1 α转录的调控机制尚不清楚。近年来发现两种长链非编码RNA（HIF 1A antisense RNA 1，HIF 1A-AS 1）和HIF 1A antisense RNA 2（HIF 1A-AS 2）对HIF-1 α mRNA的表达有调控作用，但HIF-1 α、HIF 1A-AS 1和HIF 1A-AS 2之间的调控机制尚未得到充分研究。我们推测HIF 1A-AS 1和HIF 1A-AS 2通过调节HIF-1 α在PDLCs的成骨分化中发挥重要作用。在本研究中，我们发现HIF 1A-AS 1，HIF 1A-AS 2，HIF-1 α和成骨生物标志物的表达水平在缺氧条件下具有时间依赖性。尽管HIF 1A-AS 1和HIF 1A-AS 2都与HIF-1 α mRNA互补，但只有HIF 1A-AS 2对PDLCs中的HIF-1 α表现出抑制作用。此外，HIF-1 α对HIF 1A-AS 1和HIF 1A-AS 2具有正调节作用。HIF-1 α促进PDLCs向成骨细胞分化，HIF 1A-AS 2对PDLCs向成骨细胞分化有负作用。总之，本研究揭示了HIF 1A-AS 1、HIF 1A-AS 2和HIF-1 α之间的复杂关系，以及它们在调节PDLCs成骨分化中的作用。本研究结果为正畸牙移动过程中促进牙周组织再生修复提供了理论依据。
Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is essential for regulating the osteogenic differentiation of periodontal ligament cells (PDLCs). The regulatory mechanism of HIF-1 alpha transcription is still not clear. Recently, two long non-coding RNAs, HIF1A antisense RNA 1 (HIF1A-AS1) and HIF1A antisense RNA 2 (HIF1A-AS2), were found to regulate HIF-1 alpha mRNA, but the regulatory mechanisms among HIF-1 alpha, HIF1A-AS1 and HIF1A-AS2 have not been well studied. We hypothesized that HIF1A-AS1 and HIF1A-AS2 play important roles in the osteogenic differentiation of PDLCs by regulating HIF-1 alpha. In the present study, we showed that expression levels of HIF1A-AS1, HIF1A-AS2, HIF-1 alpha and osteogenic biomarkers were time-dependent under hypoxia. Even though both HIF1A-AS1 and HIF1A-AS2 were complementary to HIF-1 alpha mRNA, only HIF1A-AS2 showed an inhibitory effect on HIF-1 alpha in PDLCs. Moreover, HIF-1 alpha had positive regulatory effects on HIF1A-AS1 and HIF1A-AS2. HIF-1 alpha promoted the osteogenic differentiation of PDLCs, and HIF1A-AS2 had a negative effect on the osteogenic differentiation of PDLCs. Altogether, the present study revealed the complex relationships among HIF1A-AS1, HIF1A-AS2 and HIF-1 alpha, as well as their roles in regulating the osteogenic differentiation of PDLCs. These findings provide a theoretical basis for promoting periodontal tissue regeneration and repair during orthodontic tooth movement.