ArticleInternational journal of oral science2022
Blockade of PD-L1/PD-1 signaling promotes osteo-/odontogenic differentiation through Ras activation.
Article in International journal of oral science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 9 citations in OpenAlex.
- Selection of a novel MSC-targeted aptamer Pt-1 and its functionalized hydrogel for tissue regeneration.Materials today. Bio · 2026Article
- Pilot spatial transcriptomics of dental pulpitis suggests immune-fibroblast profiling linked to reversibility.Journal of translational medicine · 2026Article
- Using Spatial Transcriptomics to Identify a Diagnostic Molecular Signature Associated with Reversible Dental Pulpitis.Research square · 2026Article
- shRNA-based PD-1 suppression preserves memory phenotype and function of CD19-targeted CAR-T cell.Translational cancer research · 2025Article
- The regulatory effects of PD-1/PD-L1 inhibitors on bone metabolism: opportunities and challenges in osteoporosis management.Frontiers in immunology · 2025Review
- Phosphofructokinase 1 platelet isoform induces PD-L1 expression to promote glioblastoma immune evasion.Genes & genomics · 2022Article
- BACH1 regulates the proliferation and odontoblastic differentiation of human dental pulp stem cells.BMC oral health · 2022Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The programmed cell death ligand 1 (PD-L1) and its receptor programmed cell death 1 (PD-1) deliver inhibitory signals to regulate immunological tolerance during immune-mediated diseases. However, the role of PD-1 signaling and its blockade effect on human dental pulp stem cells (hDPSCs) differentiation into the osteo-/odontogenic lineage remain unknown. We show here that PD-L1 expression, but not PD-1, is downregulated during osteo-/odontogenic differentiation of hDPSCs. Importantly, PD-L1/PD-1 signaling has been shown to negatively regulate the osteo-/odontogenic differentiation of hDPSCs. Mechanistically, depletion of either PD-L1 or PD-1 expression increased ERK and AKT phosphorylation levels through the upregulation of Ras enzyme activity, which plays a pivotal role during hDPSCs osteo-/odontogenic differentiation. Treatment with nivolumab (a human anti-PD-1 monoclonal antibody), which targets PD-1 to prevent PD-L1 binding, successfully enhanced osteo-/odontogenic differentiation of hDPSCs through enhanced Ras activity-mediated phosphorylation of ERK and AKT. Our findings underscore that downregulation of PD-L1 expression accompanies during osteo-/odontogenic differentiation, and hDPSCs-intrinsic PD-1 signaling inhibits osteo-/odontogenic differentiation. These findings provide a significant basis that PD-1 blockade could be effective immunotherapeutic strategies in hDPSCs-mediated dental pulp regeneration.
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