Differential Expression of S100A Genes in hDPSCs Following Stimulation with Two Hydraulic Calcium Silicate Cements: A Laboratory Investigation
Source abstract
Abstract
Hydraulic calcium silicate cements (HCSCs) are contemporary materials in vital pulp therapy (VPT) and regenerative endodontic therapy (RET) due to their favorable effects on pulpal and periodontal cells, including cell differentiation and hard tissue formation. Recent studies also indicated the involvement of several S100A proteins in inflammatory, differentiation, and mineralization processes of the pulp. The aim of the present study was to investigate the effects of HCSCs on S100A gene expression in human dental pulp stem cells (hDPSCs). Human DPSCs were isolated and characterized by multi-lineage stem-cell markers and differentiation protocols. In stimulation experiments hDPSCs were exposed to ProRoot®MTA, Biodentine®, IL-1β, and dexamethasone. Cell viability was determined by XTT assay. IL-6 and IL-8 mRNA expression was measured to analyze proinflammatory response. In addition, odontogenic differentiation and biomineralization assays were conducted (DSPP- and ALP-mRNA expression, ALP activity, and Alizarin Red staining). Differential expression of 13 S100A genes was examined using qPCR. Low concentrations of HCSCs enhanced the proliferation of hDPSCs, whereas higher concentrations exhibited cytotoxic effects. HCSCs induced a pro-inflammatory response and led to odontogenic differentiation and biomineralization. This was accompanied by significant alterations in the expression levels of various S100A genes. ProRoot®MTA and Biodentine® significantly affect the expression of several S100A genes in hDPSCs, supporting their role in inflammation, differentiation, and mineralization. These findings indicate a link between the effects of HCSCs on human pulp cells during VPT or RET and S100A proteins.
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Research context
OpenAlex topics: Endodontics and Root Canal Treatments · Bone and Dental Protein Studies · Oral microbiology and periodontitis research
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Periodontology, Operative and Preventive Dentistry, University Hospital, Faculty of Medicine, University of Bonn, Welschnonnenstr. 17, 53111 Bonn, Germany
Department of Prosthodontics, Preclinical Education and Material Sciences, University Hospital, Faculty of Medicine, University of Bonn, Welschnonnenstr. 17, 53111 Bonn, Germany
References (89)
Show source-provided references
1. Present Status and Future Directions—Vital Pulp Treatment and Pulp Preservation Strategies10.1111/iej.13688 ↗
2. Treatment of Pulpal and Apical Disease: The European Society of Endodontology (ESE) S3-level Clinical Practice Guideline10.1111/iej.13974 ↗
3. Mineral Trioxide Aggregate: A Comprehensive Literature Review—Part III: Clinical Applications, Drawbacks, and Mechanism of Action10.1016/j.joen.2009.09.009 ↗
4. Mineral Trioxide Aggregate: A Comprehensive Literature Review—Part II: Leakage and Biocompatibility Investigations10.1016/j.joen.2009.09.010 ↗
5. Three-Dimensional Culture of Dental Pulp Stem Cells in Direct Contact to Tricalcium Silicate Cements10.1007/s00784-015-1515-3 ↗
6. Revascularization of Immature Permanent Teeth with Apical Periodontitis: New Treatment Protocol?10.1097/00004770-200404000-00003 ↗
7. Diagnosis and Treatment of Extracanal Invasive Resorption10.1016/S0099-2399(98)80056-3 ↗
8. Present Status and Future Directions: Hydraulic Materials for Endodontic Use10.1111/iej.13709 ↗
9. Use of Mineral Trioxide Aggregate for Repair of Furcal Perforations10.1016/S1079-2104(05)80313-0 ↗
10. Cementoblasts Maintain Expression of Osteocalcin in the Presence of Mineral Trioxide Aggregate10.1097/00004770-200306000-00007 ↗
11. Histological, Ultrastructural and Quantitative Investigations on the Response of Healthy Human Pulps to Experimental Capping with Mineral Trioxide Aggregate: A Randomized Controlled Trial10.1111/j.1365-2591.2009.01558.x ↗
12. Response of Human Dental Pulp Capped with Biodentine and Mineral Trioxide Aggregate10.1016/j.joen.2013.01.005 ↗
13. A Comparative Histological Analysis of Human Pulp Following Direct Pulp Capping with Propolis, Mineral Trioxide Aggregate and Dycal10.1111/j.1834-7819.2009.01179.x ↗
14. Histological Evaluation of Mineral Trioxide Aggregate and Calcium Hydroxide in Direct Pulp Capping of Human Immature Permanent Teeth
15. Identification of a Calcium-Sensing Receptor in Human Dental Pulp Cells That Regulates Mineral Trioxide Aggregate–Induced Mineralization10.1016/j.joen.2019.03.019 ↗
16. The Ionic Products from Mineral Trioxide Aggregate–Induced Odontogenic Differentiation of Dental Pulp Cells via Activation of the Wnt/β-Catenin Signaling Pathway10.1016/j.joen.2016.04.019 ↗
17. Expression of Mineralization Markers during Pulp Response to Biodentine and Mineral Trioxide Aggregate10.1016/j.joen.2015.12.018 ↗
18. Effect of Nifedipine on the Differentiation of Human Dental Pulp Cells Cultured with Mineral Trioxide Aggregate10.1016/j.joen.2012.12.037 ↗
19. Mineral Trioxide Aggregate Promotes Odontoblastic Differentiation via Mitogen-Activated Protein Kinase Pathway in Human Dental Pulp Stem Cells10.1007/s11033-011-0728-z ↗
20. Gene Expression Profiling Concerning Mineralization in Human Dental Pulp Cells Treated with Mineral Trioxide Aggregate10.1016/j.joen.2010.08.028 ↗
21. Effects of Mineral Trioxide Aggregate on Human Dental Pulp Cells after Pulp-Capping Procedures10.1016/j.joen.2010.02.013 ↗
22. Direct Contact with Mineral Trioxide Aggregate Activates and Differentiates Human Dental Pulp Cells10.1016/j.joen.2011.09.012 ↗
23. Cytotoxicity of NeoMTA Plus, ProRoot MTA and Biodentine on Human Dental Pulp Stem Cells10.1016/j.jds.2020.10.009 ↗
24. The Effect of Accelerated Mineral Trioxide Aggregate on Odontoblastic Differentiation in Dental Pulp Stem Cell Niches10.1111/iej.12747 ↗
25. BiodentineTM Induces TGF-β1 Release from Human Pulp Cells and Early Dental Pulp Mineralization10.1111/j.1365-2591.2011.01995.x ↗
26. Phang, V., Malhotra, R., Chen, N.N., Min, K.-S., Yu, V.S.H., Rosa, V., and Dubey, N. (2023). Specimen Shape and Elution Time Affect the Mineralization and Differentiation Potential of Dental Pulp Stem Cells to Biodentine. J. Funct. Biomater., 15.10.3390/jfb15010001 ↗
27. Human Dental Pulp Cells Response to Mineral Trioxide Aggregate (MTA) and MTA Plus: Cytotoxicity and Gene Expression Analysis10.1111/iej.12683 ↗
28. The Effect of Mineral Trioxide Aggregate on Odontogenic Differentiation in Dental Pulp Stem Cells10.1016/j.joen.2012.11.004 ↗
29. S100: A Multigenic Family of Calcium-Modulated Proteins of the EF-Hand Type with Intracellular and Extracellular Functional Roles10.1016/S1357-2725(01)00046-2 ↗
30. Functions of S100 Proteins10.2174/156652413804486214 ↗
31. The Importance of Ca2+/Zn2+ Signaling S100 Proteins and RAGE in Translational Medicine
32. S100 Proteins in Mouse and Man: From Evolution to Function and Pathology (Including an Update of the Nomenclature)10.1016/j.bbrc.2004.07.096 ↗
33. S100 Proteins: Diagnostic and Prognostic Biomarkers in Laboratory Medicine10.1016/j.bbamcr.2018.10.015 ↗
34. Expression Profiling of S100 Proteins in Healthy and Irreversibly Inflamed Human Dental Pulps10.1016/j.joen.2022.01.002 ↗
35. Immunohistochemical Analysis of S100 Proteins in Normal and Irreversibly Inflamed Human Dental Pulps10.1016/j.joen.2023.02.003 ↗
36. Association of S100 Calcium-Binding Protein A12, Receptor for Advanced Glycation Endproducts, and Nuclear Factor-κB Expression with Inflammation in Pulp Tissues from Tooth Caries10.1111/jicd.12290 ↗
37. S100 and Cytokine Expression in Caries10.1128/IAI.72.7.4102-4108.2004 ↗
38. Komichi, S., Takahashi, Y., Okamoto, M., Ali, M., Watanabe, M., Huang, H., Nakai, T., Cooper, P., and Hayashi, M. (2019). Protein S100-A7 Derived from Digested Dentin Is a Critical Molecule for Dentin Pulp Regeneration. Cells, 8.10.3390/cells8091002 ↗
39. Novel Functional Peptide for Next-Generation Vital Pulp Therapy10.1177/00220345221135766 ↗
40. Mechanical Stress Induced S100A7 Expression in Human Dental Pulp Cells to Augment Osteoclast Differentiation10.1111/odi.13033 ↗
41. Distinguished Properties of Cells Isolated from the Dentin-Pulp Interface10.1016/j.aanat.2020.151628 ↗
42. In Vitro Biocompatibility of ICON(®) and TEGDMA on Human Dental Pulp Stem Cells10.1016/j.dental.2016.06.002 ↗
43. Effects of Basic Fibroblast Growth Factor on the Development of the Stem Cell Properties of Human Dental Pulp Cells10.1679/aohc.72.51 ↗
44. An Alizarin Red-Based Assay of Mineralization by Adherent Cells in Culture: Comparison with Cetylpyridinium Chloride Extraction10.1016/j.ab.2004.02.002 ↗
45. The MIQE Guidelines: Minimum Information for Publication of Quantitative Real-Time PCR Experiments10.1373/clinchem.2008.112797 ↗
46. Effects of Histone Acetyltransferase and Deacetylase Inhibitors on the Expression of S100A Genes after TLR4 and TLR2 Stimulation in Human Dental Pulp Cells10.1016/j.heliyon.2025.e43516 ↗
47. Human β-Defensins Differently Affect Proliferation, Differentiation, and Mineralization of Osteoblast-like MG63 Cells10.1002/jcp.22808 ↗
48. IL-6 as a Keystone Cytokine in Health and Disease10.1038/ni.3153 ↗
49. Interleukin-8: An Evolving Chemokine10.1016/j.cyto.2022.155828 ↗
50. Cytokine Production by Human Odontoblast-like Cells upon Toll-like Receptor-2 Engagement10.1016/j.imbio.2010.08.006 ↗
51. Influence of HEMA on LPS- and LTA-Stimulated IL-6 Release from Human Dental Pulp Cells10.1016/j.dental.2022.03.008 ↗
52. Anti-Inflammatory and Mineralization Effects of ProRoot MTA and Endocem MTA in Studies of Human and Rat Dental Pulps In Vitro and In Vivo10.1016/j.joen.2018.07.012 ↗
53. Effects of Calcium Silicate Endodontic Cements on Biocompatibility and Mineralization-Inducing Potentials in Human Dental Pulp Cells10.1016/j.joen.2014.01.001 ↗
54. Odontoblastic Differentiation, Inflammatory Response, and Angiogenic Potential of 4 Calcium Silicate–Based Cements: Micromega MTA, ProRoot MTA, RetroMTA, and Experimental Calcium Silicate Cement10.1016/j.joen.2015.04.018 ↗
55. The Effects of Mineral Trioxide Aggregates on Cytokine Production by Mouse Pulp Tissue10.1016/j.tripleo.2008.01.025 ↗
56. Mineral Trioxide Aggregate Suppresses Pro-inflammatory Cytokine Expression via the Calcineurin/Nuclear Factor of Activated T Cells/Early Growth Response 2 Pathway in Lipopolysaccharide-stimulated Macrophages10.1111/iej.13386 ↗
57. Yune, J.-Y., Lee, D., and Kim, S.-Y. (2023). The Combined Effects of Hydraulic Calcium Silicate Cement and Enamel Matrix Derivative Regarding Osteogenic and Dentinogenic Differentiation on Human Dental Pulp Stem Cells. Materials, 16.10.3390/ma16114003 ↗
58. Comparative Proteomic Profiling of Human Dental Pulp Stem Cells and Periodontal Ligament Stem Cells under in Vitro Osteogenic Induction10.1016/j.archoralbio.2018.01.015 ↗
59. Mineral Trioxide Aggregate Promotes the Odonto/Osteogenic Differentiation and Dentinogenesis of Stem Cells from Apical Papilla via Nuclear Factor Kappa B Signaling Pathway10.1016/j.joen.2014.01.042 ↗
60. A Correlation between Wnt/Beta-Catenin Signaling and the Rate of Dentin Secretion10.1016/j.joen.2019.07.014 ↗
61. Analysis of Hard Tissue Regeneration and Wnt Signalling in Dental Pulp Tissues after Direct Pulp Capping with Different Materials10.1111/iej.13162 ↗
62. Transcriptomic Profiling of Human Dental Pulp Cells Treated with Tricalcium Silicate–Based Cements by RNA Sequencing10.1007/s00784-020-03647-0 ↗
63. S100A2 Silencing Relieves Epithelial-Mesenchymal Transition in Pulmonary Fibrosis by Inhibiting the Wnt/β-Catenin Signaling Pathway10.1089/dna.2020.6030 ↗
64. Downregulation of S100A4 Alleviates Cardiac Fibrosis via Wnt/β -Catenin Pathway in Mice10.1159/000489683 ↗
65. S100A4 Modulates Cell Proliferation, Apoptosis and Fibrosis in the Hyperplastic Prostate10.1016/j.biocel.2024.106551 ↗
66. Icariin Ameliorates Coxsackievirus B3-Induced Viral Myocarditis by Modulating the S100 Calcium Binding Protein A6/β-Catenin/c-Myc Signaling Pathway10.1016/j.phymed.2024.156214 ↗
67. S100A6 Regulates Nucleus Pulposus Cell Apoptosis via Wnt/β-Catenin Signaling Pathway: An In Vitro and In Vivo Study10.1186/s10020-024-00853-4 ↗
68. Exosome-derived Long Non-coding RNA AC010789.1 Modified by FTO and hnRNPA2B1 Accelerates Growth of Hair Follicle Stem Cells against Androgen Alopecia by Activating S100A8/Wnt/Β-catenin Signalling10.1002/ctm2.70152 ↗
69. Duan, L., Wu, R., Ye, L., Wang, H., Yang, X., Zhang, Y., Chen, X., Zuo, G., Zhang, Y., and Weng, Y. (2013). S100A8 and S100A9 Are Associated with Colorectal Carcinoma Progression and Contribute to Colorectal Carcinoma Cell Survival and Migration via Wnt/β-Catenin Pathway. PLoS ONE, 8.10.1371/annotation/61e0cb2d-6d8c-41d7-99f2-d1b97581e207 ↗
70. S100 Calcium Binding Protein A11 (S100A11) Promotes the Proliferation, Migration and Invasion of Cervical Cancer Cells, and Activates Wnt/β-Catenin Signaling10.2147/OTT.S225248 ↗
71. S100A9 Promotes the Proliferation and Migration of Cervical Cancer Cells by Inducing Epithelial-mesenchymal Transition and Activating the Wnt/Β-catenin Pathway
72. S100A16 Promotes Acute Kidney Injury by Activating HRD1-Induced Ubiquitination and Degradation of GSK3β and CK1α10.1007/s00018-022-04213-5 ↗
73. Role of S100A1 in Hypoxia-Induced Inflammatory Response in Cardiomyocytes via TLR4/ROS/NF-κB Pathway10.1111/jphp.12415 ↗
74. The Metastasis-Associated Protein S100A4 Promotes the Inflammatory Response of Mononuclear Cells via the TLR4 Signalling Pathway in Rheumatoid Arthritis10.1093/rheumatology/keu031 ↗
75. Mechanism of S100A9-Mediated Astrocyte Activation via TLR4/NF-κB in Parkinson’s Disease10.1016/j.intimp.2024.113938 ↗
76. Calprotectin (S100A8/S100A9): A Key Protein between Inflammation and Cancer10.1007/s00011-018-1173-4 ↗
77. Inhibition of S100A9 Alleviates Neurogenic Pulmonary Edema after Subarachnoid Hemorrhage10.1016/j.bcp.2023.115905 ↗
78. Alarmins S100A8/A9 Promote Intervertebral Disc Degeneration and Inflammation-Related Pain in a Rat Model through Toll-like Receptor-4 and Activation of the NF-κB Signaling Pathway10.1016/j.joca.2022.03.011 ↗
79. Role of S100 Proteins in Health and Disease10.1016/j.bbamcr.2020.118677 ↗
80. Gong, N., Shi, L., Bing, X., Li, H., Hu, H., Zhang, P., Yang, H., Guo, N., Du, H., and Xia, M. (2022). S100A4/TCF Complex Transcription Regulation Drives Epithelial-Mesenchymal Transition in Chronic Sinusitis Through Wnt/GSK-3β/β-Catenin Signaling. Front. Immunol., 13.10.3389/fimmu.2022.835888 ↗
81. S100A4-Induced Cell Motility and Metastasis Is Restricted by the Wnt/β-Catenin Pathway Inhibitor Calcimycin in Colon Cancer Cells10.1091/mbc.e10-09-0739 ↗
82. The Metastasis-Associated Gene S100A4 Is a Novel Target of β-Catenin/T-Cell Factor Signaling in Colon Cancer10.1053/j.gastro.2006.08.041 ↗
83. Smad3 and Bmal1 Regulate P21 and S100A4 Expression in Myocardial Stromal Fibroblasts via TNF-α10.1007/s00418-017-1597-x ↗
84. Selective PPARα Agonist Pemafibrate Inhibits TNF-α-Induced S100A7 Upregulation in Keratinocytes10.1016/j.jdermsci.2020.05.005 ↗
85. Pro-Inflammatory S100A8 and S100A9 Proteins: Self-Assembly into Multifunctional Native and Amyloid Complexes10.3390/ijms13032893 ↗
86. Induction of Periodontal Ligament–like Cells by Coculture of Dental Pulp Cells, Dedifferentiated Cells Generated from Epithelial Cell Rests of Malassez, and Umbilical Vein Endothelial Cells10.1016/j.joen.2022.08.006 ↗
87. S100A4 Is Expressed in Human Odontoblasts and Odontoblast-like Cells10.1016/j.tice.2022.101959 ↗
88. S100A4: A Novel Negative Regulator of Mineralization and Osteoblast Differentiation10.1359/jbmr.2003.18.3.493 ↗
89. Insulin Receptor Deletion in S100a4-Lineage Cells Accelerates Age-Related Bone Loss10.1016/j.bonr.2019.100197 ↗