Transcriptomic Analysis of Alveolar Bone Mesenchymal Stem Cells in Cleidocranial Dysplasia
- Sermporn Thaweesapphithak, Annop Krasaesin, Kanokwan Sriwattanapong, Kanokrat Sriwangyang, Mohamed El-Tanani, Syed Arman Rabbani, Sung-Dae Cho, Anand Marya, Chawan Manaspon, Hamid Alinejad-Rokny, Thantrira Porntaveetus
- https://doi.org/10.1016/j.identj.2026.111223
Abstract
Objectives
Cleidocranial dysplasia (CCD) is a rare skeletal disorder caused by RUNX2 variants, clinically characterized by unerupted teeth and impaired alveolar bone remodelling. This study aimed to profile the transcriptomic landscape of alveolar bone-derived mesenchymal stem cells (aBMSCs) isolated from CCD patients to identify molecular alterations underlying their osteogenic impairment.
Materials and methods
Primary aBMSCs were isolated from CCD patients harbouring pathogenic RUNX2 variants and age-matched controls. Flow cytometry confirmed canonical MSC markers and sample purity. Cells were cultured under basal and osteogenic conditions. Bulk RNA-sequencing of CCD–control pairs ( n = 4) identified differential gene expression and pathway dysregulation. Selected candidate genes were further examined by qRT-PCR using the same two CCD donors and additional age-matched control samples ( n = 6).
Results
Transcriptomic profiling revealed that CCD aBMSCs exhibit alterations in extracellular matrix (ECM)-related pathways, specifically the downregulation of COL1A1, COL3A1 , and COL5A1. Differentially expressed genes were highly enriched for G protein–coupled receptor and prostaglandin signalling cascades, suggesting potential alterations in regulatory networks associated with osteogenic differentiation. Upon osteogenic induction, CCD aBMSCs demonstrated osteogenic induction-associated transcriptional changes. PPP1R12B and PTGER2 were identified as candidate genes associated with baseline CCD-related differences and osteogenic induction-associated changes within CCD aBMSCs.
Conclusion
This exploratory study suggests that CCD aBMSCs exhibit transcriptomic alterations involving ECM-related genes and signalling pathways associated with osteogenic differentiation. These candidate molecular changes may contribute to impaired alveolar bone remodelling in CCD and require further validation in larger cohorts and functional studies.