Stem cell regulatory gene expression in human adult dental pulp and periodontal ligament cells undergoing odontogenic/osteogenic differentiation.
BACKGROUND
During development and regeneration, odontogenesis and osteogenesis are initiated by a cascade of signals driven by several master regulatory genes.


METHODS
In this study, we investigated the differential expression of 84 stem cell-related genes in dental pulp cells (DPCs) and periodontal ligament cells (PDLCs) undergoing odontogenic/osteogenic differentiation.


RESULTS
Our results showed that, although there was considerable overlap, certain genes had more differential expression in PDLCs than in DPCs. CCND2, DLL1, and MME were the major upregulated genes in both PDLCs and DPCs, whereas KRT15 was the only gene significantly downregulated in PDLCs and DPCs in both odontogenic and osteogenic differentiation. Interestingly, a large number of regulatory genes in odontogenic and osteogenic differentiation interact or crosstalk via Notch, Wnt, transforming growth factor beta (TGF-beta)/bone morphogenic protein (BMP), and cadherin signaling pathways, such as the regulation of APC, DLL1, CCND2, BMP2, and CDH1. Using a rat dental pulp and periodontal defect model, the expression and distribution of both BMP2 and CDH1 have been verified for their spatial localization in dental pulp and periodontal tissue regeneration.


CONCLUSIONS
This study has generated an overview of stem cell-related gene expression in DPCs and PDLCs during odontogenic/osteogenic differentiation and revealed that these genes may interact through the Notch, Wnt, TGF-beta/BMP, and cadherin signaling pathways to play a crucial role in determining the fate of dental derived cell and dental tissue regeneration. These findings provided a new insight into the molecular mechanisms of the dental tissue mineralization and regeneration.
Department of Operative Dentistry, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, Guangdong, China.
Lu
L
Liu
Junqi
J
Ling
Xi
X
Wei
Liping
L
Wu
Yin
Y
Xiao
D000328:Adult; D000539:Alveolar Process / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D015703:Antigens, CD; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D056742:Cyclin D2 / Q000235:genetics; D003739:Dental Cementum / Q000473:pathology / Q000503:physiopathology; D003782:Dental Pulp / Q000166:cytology* / Q000293:injuries / Q000502:physiology; D003804:Dentin / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics*; D017491:Genes, APC / Q000502:physiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D053569:Keratin-15 / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D015260:Neprilysin / Q000235:genetics; D009805:Odontogenesis / Q000235:genetics*; D010012:Osteogenesis / Q000235:genetics*; D010513:Periodontal Ligament / Q000166:cytology* / Q000293:injuries / Q000502:physiology; D051381:Rats; D020239:Receptor Cross-Talk / Q000502:physiology; D051880:Receptors, Notch / Q000235:genetics; D012038:Regeneration / Q000235:genetics; D013234:Stem Cells / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics
D015703:Antigens, CD; C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; C080336:CCND2 protein, human; C513384:CDH1 protein, human; D015820:Cadherins; D002135:Calcium-Binding Proteins; D056742:Cyclin D2; C512941:DLK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C116015:KRT15 protein, human; D053569:Keratin-15; D008565:Membrane Proteins; D051880:Receptors, Notch; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D007334:Insulin-Like Growth Factor I; D015260:Neprilysin