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X-Box Binding Protein 1 Regulates Osteogenesis of Periodontal Ligament Cells During Aging by Modulating P53 Signaling
Youli Zheng1, Mengru Zhai2,3, Xijing Bai2,3
1The School and Hospital of Stomatology, Tianjin Medical University, Tianjin, 300070, China, tijmu.edu.cn.
Stem Cells International
|April 13, 2026
Summary
Aging impairs periodontal ligament stem cell differentiation. X-box binding protein 1 (XBP1) upregulation reverses this by modulating the P53/P21 pathway, crucial for osteogenic differentiation in aging cells.
Area of Science:
- Cell Biology
- Stem Cell Research
- Aging Research
Background:
- Aging negatively impacts periodontal ligament stem cells' (PDLSCs) ability to differentiate into bone cells.
- The precise molecular mechanisms underlying age-related decline in PDLSC osteogenic differentiation remain largely unknown.
- X-box binding protein 1 (XBP1), a key transcription factor involved in cellular senescence, is hypothesized to play a role.
Purpose of the Study:
- To investigate the role of XBP1 in the osteogenic differentiation of PDLSCs during aging.
- To elucidate the underlying molecular mechanisms connecting XBP1, aging, and PDLSC osteogenic potential.
Main Methods:
- Compared young (Y-PDLSCs) and elderly PDLSCs (E-PDLSCs) for senescence and osteogenic markers.
- Quantified XBP1 expression using RT-PCR and Western Blotting.
- Modulated XBP1 levels via lentiviral vectors (pLVX-XBP1 for upregulation, shXBP1 for downregulation) and assessed effects on PDLSC senescence and osteogenic differentiation. Investigated XBP1 target genes and pathways, including the P53/P21 pathway, using database analysis and PFTα inhibition.
Main Results:
- Elderly PDLSCs exhibited increased senescence markers, cell cycle suppression, and reduced osteogenic differentiation compared to young PDLSCs.
- XBP1 expression decreased with age in PDLSCs; XBP1 upregulation partially restored aging PDLSC function.
- XBP1 overexpression facilitated osteogenic differentiation, and its target genes were linked to the P53/P21 pathway, which was downregulated upon XBP1 upregulation. Inhibiting P53/P21 partially rescued osteogenic differentiation impaired by XBP1 knockdown.
Conclusions:
- XBP1 is a critical regulator of PDLSC osteogenic differentiation in the context of aging.
- XBP1 exerts its function, at least partly, through the modulation of the P53/P21 signaling pathway.
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