LncRNA GAS5 regulates osteogenic differentiation of human periodontal ligament stem cells through miR-23b-3p/STAT5B axis.

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.