Mechanical force-sensitive lncRNA SNHG8 inhibits osteogenic differentiation by regulating EZH2 in hPDLSCs

Long non-coding RNAs (lncRNAs) play important roles in various physiological and pathophysiological processes. However, the effect of mechanical force on lncRNAs and their role in osteogenic differentiation of periodontal ligament stem cells (PDLSCs) remains unclear. Here, we showed that the expression of lncRNA small nucleolar RNA host gene 8 (SNHG8) was steadily declined in PDLSCs under mechanical force. This reduced expression of SNHG8 promoted osteogenic differentiation of PDLSCs under mechanical force. After knockdown of SNHG8 by shRNA, the expression of osteogenic-related genes was increased in PDLSCs under mechanical force. Regarding the osteogenic regulatory ability of SNHG8, PDLSCs with lower level of expression of SNHG8 under osteogenic induction had a higher level of expression of osteogenic-related genes, higher level of alkaline phosphatase (ALP), and more mineralised nodules. In rats, the expression of the homolog, Smim4, was decreased during tooth movement. PDLSCs with lower expression of SNHG8 in nude mice also showed better bone formation ability during ectopic osteogenesis. Mechanistically, downregulation of SNHG8 led to lower expression of enhancer of zeste homolog 2 (EZH2), which negatively regulated the osteogenic differentiation of PDLSCs. Our study indicated that the mechanically sensitive lncRNA SNHG8 regulates the osteogenic differentiation of PDLSCs through epigenetic pathways. Our results provided solid evidence for the regulation of cell differentiation by non-coding genes, which might serve as potential therapeutic targets for bone reconstruction or periodontal tissue regeneration during orthodontics.