Comparison of HIF1A‑AS1 and HIF1A‑AS2 in regulating HIF‑1α and the osteogenic differentiation of PDLCs under hypoxia.

Hypoxia‑inducible factor‑1α (HIF‑1α) is essential for regulating the osteogenic differentiation of periodontal ligament cells (PDLCs). The regulatory mechanism of HIF‑1α 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‑1α mRNA, but the regulatory mechanisms among HIF‑1α, 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‑1α. In the present study, we showed that expression levels of HIF1A‑AS1, HIF1A‑AS2, HIF‑1α and osteogenic biomarkers were time‑dependent under hypoxia. Even though both HIF1A‑AS1 and HIF1A‑AS2 were complementary to HIF‑1α mRNA, only HIF1A‑AS2 showed an inhibitory effect on HIF‑1α in PDLCs. Moreover, HIF‑1α had positive regulatory effects on HIF1A‑AS1 and HIF1A‑AS2. HIF‑1α 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‑1α, 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.