Background and Objective Aging impairs the osteogenic differentiation of periodontal ligament stem cells (PDLSCs), but the mechanism is unclear. X‐box binding protein 1 (XBP1), a transcription factor affecting cell senescence, may be involved. This study focuses on the role and mechanism of XBP1 in PDLSCs’ osteogenic differentiation during aging. Methods Young PDLSCs (Y‐PDLSCs) and elderly PDLSCs (E‐PDLSCs) were obtained. XBP1 expression was quantified using both real‐time polymerase chain reaction (RT‐PCR) and western blotting (WB). Lentiviral infection was employed to modulate XBP1 expression, with pLVX‐XBP1 utilized for upregulation and shXBP1 for downregulation. The degree of senescence in PDLSCs was determined using β‐galactosidase staining and cell cycle analysis. PDLSCs’ osteogenic differentiation was assessed through WB, alkaline phosphatase (ALP), and alizarin red staining. The Gene Transcription Regulation Database (GTRD) and microarray analysis was used to identify XBP1’s target genes and potential pathways. Additionally, PFTα was applied to inhibit the P53/P21 pathway in PDLSCs. Results E‐PDLSCs had higher β‐galactosidase expression, suppressed cell cycle, and decreased osteogenic differentiation compared to Y‐PDLSCs. XBP1 expression in PDLSCs decreased with aging, and upregulation of XBP1 by pLVX‐XBP1 partially reversed this aging process. Osteogenic induction increased XBP1 expression in PDLSCs, and pLVX‐XBP1 facilitated the osteogenic differentiation of these cells. The target genes of XBP1 were enriched in the P53/P21 pathway, which was highly expressed in P9 PDLSCs but showed lower expression following XBP1 overexpression. Moreover, inhibiting the P53/P21 pathway by PFTα could partially reverse the inhibitory effect of shXBP1 on PDLSCs’ osteogenic differentiation. Conclusions XBP1 plays a pivotal role in the regulation of PDLSCs’ osteogenic differentiation during the aging process, at least in part, through the modulation of the P53/P21 pathway.
Zheng et al. (Thu,) studied this question.