Periodontal ligament stem cells (PDLSCs) play a crucial role in alveolar bone regeneration due to their inherent osteogenic differentiation capacity. However, the molecular mechanisms regulating PDLSC osteogenic differentiation remain incompletely understood. In this study, human PDLSCs were isolated and characterized, revealing that the cytoplasmic long non-coding RNA GAS5 was significantly upregulated during osteogenic induction. Functional assays demonstrated that GAS5 overexpression markedly enhanced alkaline phosphatase (ALP) activity, mineralized nodule formation, and the expression of osteogenic marker genes (RUNX2, OCN, OPN). Conversely, GAS5 knockdown attenuated these osteogenic phenotypes. Mechanistically, GAS5 functioned as a competitive endogenous RNA (ceRNA) by directly binding to miR-23b-3p, thereby preventing miR-23b-3p-mediated post-transcriptional silencing of its target gene STAT5B. Rescue experiments confirmed that STAT5B silencing abolished the pro-osteogenic effects induced by GAS5 overexpression, while miR-23b-3p inhibition reversed the osteogenic impairment caused by GAS5 knockdown. Collectively, our findings reveal a novel regulatory axis (GAS5/miR-23b-3p/STAT5B) that modulates PDLSC osteogenic differentiation, offering a potential therapeutic target for periodontal tissue regeneration strategies. • GAS5 sponges miR-23b-3p, promoting osteogenic differentiation in PDLSCs. • miR-23b-3p targets STAT5B; repressed by GAS5, upregulating STAT5B. • Overexpression of GAS5 or inhibition of miR-23b-3p enhances osteogenesis in PDLSCs. • Knockdown of GAS5 or overexpression of miR-23b-3p suppresses osteogenesis in PDLSCs. • Targeting the GAS5/miR-23b-3p/STAT5B axis offers a promising therapeutic strategy for regenerating periodontal tissue and alveolar bone.
Zhou et al. (Sun,) studied this question.