Knockdown of Bach1 protects periodontal bone regeneration from inflammatory damage

Abstract

Periodontal bone regeneration is a major challenge in the treatment of periodontitis. However, the regenerative vitality of periodontal ligament cells (PDLCs) declines in the environment of periodontitis and accompanying oxidative stress. This study aimed to investigate the functional mechanisms of Bach1, a transcriptional suppressor involved in oxidative stress response, and its regulation of PDLC osteogenesis under inflammatory conditions. We observed a significant elevation in Bach1 expression in periodontal tissues with periodontitis and PDLCs under inflammatory conditions. Knockdown of Bach1 alleviated the inflammation-induced oxidative stress level and partly offset the inhibitory effect of inflammatory conditions on osteogenesis, as well as the expression of osteogenic genes BMP6, OPG and RUNX2. Similarly, knockdown of Bach1 protects PDLCs from inflammatory damage to periodontal bone regeneration in vivo. Furthermore, we found that Bach1 could bind to the histone methyltransferase EZH2, and the binding increased under inflammatory conditions. Bach1 enhanced the ability of EZH2 to catalyse H3K27me3 on the promoter region of RUNX2 and BMP6, thus repressing the expression of osteoblastic genes. In conclusion, our study revealed that knockdown of Bach1 effectively rescued the osteogenesis and oxidative stress of PDLCs with inflammation. Bach1 could be a promising target for enhancing periodontal tissue regeneration under periodontitis conditions.

Keywords: Bach1; osteogenesis; oxidative stress; periodontal ligament cells (PDLCs); periodontitis.