Background: Exploring the effects of lncRNA SNHG1 in the process of osteogenic differentiation of periodontal ligament stem cells (PDLSCs) would provide novel therapeutic strategies for tissue regeneration.

Methods: Loss-of-function and gain-of-function assays were induced by lentivirus. The osteogenic differentiation of PDLSCs were assessed by ALP staining and Alizarin Red staining as well as the mRNA and protein levels of osteogenic marker genes osterix, osteocalcin, and alkaline phosphatase through qRT-PCR and western blot. RNA immunoprecipitation assay and chromatin immunoprecipitation assays were performed to uncover the interaction between SNHG1 and EZH2.

Results: Our analysis revealed that SNHG1 was downregulated and KLF2 was upregulated during the osteogenic induction differentiation of PDLSCs. SNHG1 inhibited while KLF2 promoted osteogenic differentiation of PDLSCs. SNHG1 directly interact with the histone methyltransferase enhancer of the zeste homolog 2 (EZH2) and modulate the histone methylation of promoter of Kruppel-like factor 2 (KLF2) and altered the progress osteogenic differentiation of PDLSCs.

Conclusions: Taken together, SNHG1 inhibited the osteogenic differentiation of PDLSCs through EZH2-mediated H3K27me3 methylation of KLF2 promotor and provided a novel class of therapeutic targets for regenerate dental tissues.