Integrin-Associated Signalling Regulates Jagged1-Induced Osteogenic Differentiation of Human Dental Pulp Stem Cells
INTERNATIONAL DENTAL JOURNAL, cilt.76, sa.5, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 76 Sayı: 5
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.identj.2026.109808
- Dergi Adı: INTERNATIONAL DENTAL JOURNAL
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CINAHL, Directory of Open Access Journals, Natural Science Collection (ProQuest), Biological Science Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
- İstanbul Üniversitesi Adresli: Evet
Özet
Aim: To investigate the role of integrin-associated adhesion signalling in Jagged1-driven osteogenic differentiation and to determine the specific contribution of integrin /33 (ITG/33).
Methodology: RNA sequencing data from Jagged1-activated human dental pulp cells were analysed to identify changes in integrin-associated signalling. Jagged1-induced Notch activation and ITG/33 expression were validated by quantitative real-time polymerase chain reaction and immunofluorescence. Functional inhibition of integrin activity was performed using the av/33 antagonist cilengitide, and the specific role of ITG/33 was examined using ITG/33-targeting siRNA. Apoptosis was evaluated by flow cytometry, migration by a wound-healing assay, and osteogenic differentiation by Alizarin Red S staining and osteogenic gene expression.
Results: RNA sequencing analysis revealed enrichment of extracellular matrix-and integrin-associated pathways among Jagged1-responsive genes in human dental pulp stem cells (hDPSCs), with ITG/33 identified as a prominently upregulated integrin subunit. Jagged1 induced ITGB3 mRNA expression in parallel with dose-and time-dependent increases in the Notch target genes HES1 and HEY1, and increased ITG/33 protein expression was further confirmed by immunofluorescence. Pharmacological inhibition with cilengitide did not affect viability, proliferation, or migration, but significantly suppressed basal and Jagged1-induced mineralisation and reduced RUNX2 expression. High-dose cilengitide (1000 nM) increased late-stage apoptosis under Jagged1 stimulation. In contrast, ITGB3 silencing attenuated basal osteogenic differentiation but did not impair Jagged1-induced mineralisation. Conclusion: Jagged1-induced osteogenic differentiation of hDPSCs requires integrin-dependent adhesion signalling but is not exclusively dependent on ITGB3 transcription. These findings support integrin-Notch crosstalk as a regulatory mechanism in hDPSC osteogenesis and provide a rationale for designing regenerative dental biomaterials that combine Notch-activating and adhesion-supportive cues.
(c) 2026 The Authors. Published by Elsevier Inc. on behalf of FDI World Dental Federation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)