EC Dental Science

Research Article Volume 22 Issue 3 - 2023

Dental Pulp Stem Cell Differentiation Potential of BMP-2 and BMP-4

David Li1, Hyewon Lee2, David Foote2 and Karl Kingsley3*

1Orthodontic Resident in the Department of Advanced Education in Orthodontics at the University of Nevada, Las Vegas - School of Dental Medicine, Las Vegas, Nevada, USA
2Second-Year Dental Student in the Department of Clinical Sciences at the University of Nevada, Las Vegas - School of Dental Medicine, Las Vegas, Nevada, USA
3Professor of Biomedical Sciences at the University of Nevada, Las Vegas - School of Dental Medicine, Las Vegas, Nevada, USA

*Corresponding Author: Karl Kingsley, Professor of Biomedical Sciences at the University of Nevada, Las Vegas - School of Dental Medicine, Las Vegas, Nevada, USA.
Received: February 10, 2023; Published: February 18, 2023

Introduction: Many studies are now evaluating the potential for dental pulp stem cells (DPSC) to assist with more complex and biotechnology applications, such as facilitating and promoting osseointegration following dental implants. However, the effects of factors that may control osseointegration and bone repair using DPSC including bone morphogenic proteins (BMP-2, BMP-4) are not yet well understood. Based upon this lack of evidence, the primary goal of this project is to evaluate the potential effects of BMPs (alone or in combination with other growth factors) to induce factors associated with osteogenesis.

Methods: DPSC isolates from an existing repository (n = 13) were plated into 96-well experimental assays with the addition of BMP-2, BMP-4 or a combination. Viability and growth assays were performed and RNA was collected and screened using quantitative polymerase chain reaction (qPCR).

Results: BMP-2 administration induced increased proliferation and viability among two rapidly dividing DPSC isolates, while administration of BMP-4 induced similar responses among different rapid and all the intermediate dividing DPSC isolates. The combination of BMP-2 and BMP-4 induced differential increases in growth and viability among a distinct subset of rapidly and slowly dividing DPSC isolates that did not respond to the isolated administration of BMP-2 or BMP-4 alone. In addition, the increased growth and proliferation among these distinct isolates was associated with increased expression of alkaline phosphatase (ALP).

Conclusion: These results suggest that BMP-2 and BMP-4 (both alone and in combination) are sufficient to induce the production of the early bone biomarkers ALP within specific subsets of the DPSC isolates evaluated. Although these results represent a significant step towards our understanding of DPSC biology, further research will be needed to determine the additional factors and biomarkers that may facilitate osteogenic differentiation.

Keywords: Dental Pulp Stem Cells (DPSC); BMP-2, BMP-4; Quantitative Polymerase Chain Reaction (qPCR); Alkaline Phosphatase (ALP)

  1. Tam PKH., et al. “Regenerative medicine: postnatal approaches”. The Lancet Child and Adolescent Health 9 (2022): 654-666.
  2. Firoozi P., et al. “The Role of Photobiomodulation on Dental-Derived Mesenchymal Stem Cells in Regenerative Dentistry: A Comprehensive Systematic Review”. Current Stem Cell Research and Therapy (2022).
  3. Hoang DM., et al. “Stem cell-based therapy for human diseases”. Signal Transduction and Targeted Therapy 1 (2022): 272.
  4. Arjmand B., et al. “Advancement of Organoid Technology in Regenerative Medicine”. Regenerative Engineering and Translational Medicine 8 (2022): 1-14.
  5. Pradhan AU., et al. “A review of stem cell therapy: An emerging treatment for dementia in Alzheimer's and Parkinson's disease”. Brain and Behavior 15 (2022): e2740.
  6. Costela-Ruiz VJ., et al. “Different Sources of Mesenchymal Stem Cells for Tissue Regeneration: A Guide to Identifying the Most Favorable One in Orthopedics and Dentistry Applications”. International Journal of Molecular Sciences 11 (2022): 6356.
  7. Roato I., et al. “Oral Cavity as a Source of Mesenchymal Stem Cells Useful for Regenerative Medicine in Dentistry”. Biomedicines9 (2021): 1085.
  8. Margiana R., et al. “Clinical application of mesenchymal stem cell in regenerative medicine: a narrative review”. Stem Cell Research and Therapy 1 (2022): 366.
  9. Fan XL., et al. “Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy”. Cellular and Molecular Life Sciences 14 (2020): 2771-2794.
  10. Klimczak A. “Mesenchymal Stem/Progenitor Cells and Their Derivates in Tissue Regeneration”. International Journal of Molecular Sciences 12 (2020): 6652.
  11. Maqsood M., et al. “Adult mesenchymal stem cells and their exosomes: Sources, characteristics, and application in regenerative medicine”. Life Sciences 256 (2020): 118002.
  12. Mishra VK., et al. “Identifying the Therapeutic Significance of Mesenchymal Stem Cells”. Cells5 (2020): 1145.
  13. Jakob M., et al. “Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Show Comparable Functionality to Their Autologous Origin”. Cells1 (2020): 33.
  14. Dzobo K. “Recent Trends in Multipotent Human Mesenchymal Stem/Stromal Cells: Learning from History and Advancing Clinical Applications”. OMICS6 (2021): 342-357.
  15. Nancarrow-Lei R., et al. “A Systemic Review of Adult Mesenchymal Stem Cell Sources and their Multilineage Differentiation Potential Relevant to Musculoskeletal Tissue Repair and Regeneration”. Current Stem Cell Research and Therapy 8 (2017): 601-610.
  16. Kobolak J., et al. “Mesenchymal stem cells: Identification, phenotypic characterization, biological properties and potential for regenerative medicine through biomaterial micro-engineering of their niche”. Methods 99 (2016): 62-68.
  17. Yamagishi H and Shigematsu K. “Perspectives on Stem Cell-Based Regenerative Medicine with a Particular Emphasis on Mesenchymal Stem Cell Therapy”. JMAJ - Japan Medical Association 1 (2022): 36-43.
  18. Yamagishi H and Shigematsu K. “Perspectives on Stem Cell-Based Regenerative Medicine with a Particular Emphasis on Mesenchymal Stem Cell Therapy”. JMAJ - Japan Medical Association 1 (2022): 36-43.
  19. Samiei M., et al. “Application of collagen and mesenchymal stem cells in regenerative dentistry”. Current Stem Cell Research and Therapy (2021).
  20. Hsiao HY., et al. “Application of dental stem cells in three-dimensional tissue regeneration”. World Journal of Stem Cells 11 (2021): 1610-1624.
  21. Irfan M., et al. “The role of complement C5a receptor in DPSC odontoblastic differentiation and in vivo reparative dentin formation”. International Journal of Oral Science 1 (2022): 7.
  22. Hao J., et al. “IGFBP5 enhances the dentinogenesis potential of dental pulp stem cells via JNK and ErK signalling pathways”. Journal of Oral Rehabilitation 12 (2020): 1557-1565.
  23. Li Q., et al. “NBCe1 Regulates Odontogenic Differentiation of Human Dental Pulp Stem Cells via NF-κB”. International Journal of Stem Cells (2022).
  24. Li C., et al. “Neu5Ac Induces Human Dental Pulp Stem Cell Osteo-/Odontoblastic Differentiation by Enhancing MAPK/ERK Pathway Activation”. Stem Cells International (2021): 5560872.
  25. Kotova AV., et al. “Comparative Analysis of Dental Pulp and Periodontal Stem Cells: Differences in Morphology, Functionality, Osteogenic Differentiation and Proteome”. Biomedicines 11 (2021): 1606.
  26. Xie H., et al. “CVD-grown monolayer graphene induces osteogenic but not odontoblastic differentiation of dental pulp stem cells”. Dental Materials Journal 1 (2017): e13-e21.
  27. Tóth F., et al. “Effect of inducible bone morphogenetic protein 2 expression on the osteogenic differentiation of dental pulp stem cells in vitro”. Bone 132 (2020): 115214.
  28. Hrubi E., et al. “Diverse effect of BMP-2 homodimer on mesenchymal progenitors of different origin”. Human Cell 2 (2018): 139-148.
  29. Cinelli J., et al. “Assessment of dental pulp stem cell (DPSC) biomarkers following induction with bone morphogenic protein (BMP-2)”. Journal of Advances in Biology and Biotechnology 2 (2018): 1-12.
  30. Cinelli J., et al. “Differential Effects of Bone Morphogenic Protein (BMP) and Vascular Endothelial Growth Factor (VEGF) on Dental Pulp Stem Cell (DPSC) Subpopulations”. EC Dental Science 3 (2020): 01-10.
  31. Bae S., et al. “Characterization of Dental Pulp Stem Cell Responses to Functional Biomaterials Including Mineralized Trioxide Aggregates”. Journal of Functional Biomaterials 1 (2021): 15.
  32. Salhotra A., et al. “Mechanisms of bone development and repair”. Nature Reviews Molecular Cell Biology 11 (2020): 696-711.
  33. Da Silva Madaleno C., et al. “BMP signalling in a mechanical context - Implications for bone biology”. Bone 137 (2020): 115416.
  34. Rahman MS., et al. “TGF-β/BMP signaling and other molecular events: regulation of osteoblastogenesis and bone formation”. Bone Research 3 (2015): 15005.
  35. Wu M., et al. “TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease”. Bone Research 4 (2016): 16009.
  36. Kaspiris A., et al. “Therapeutic Efficacy and Safety of Osteoinductive Factors and Cellular Therapies for Long Bone Fractures and Non-Unions: A Meta-Analysis and Systematic Review”. Journal of Clinical Medicine13 (2022): 3901.
  37. Morsczeck C. “Mechanisms during Osteogenic Differentiation in Human Dental Follicle Cells”. International Journal of Molecular Sciences 11 (2022): 5945.
  38. Kolios G and Moodley Y. “Introduction to stem cells and regenerative medicine”. Respiration 1 (2013): 3-10.
  39. Tsutsui TW. “Dental Pulp Stem Cells: Advances to Applications”. Cloning and Stem Cells 13 (2020): 33-42.
  40. Tomlin A., et al. “Dental Pulp Stem Cell Biomarkers for Cellular ViabilityFollowing Long-Term Cryopreserva-tion”. The International Journal of Developmental Biology 1 (2018): 1-6.
  41. Aksel H and Huang GT. “Combined Effects of Vascular Endothelial Growth Factor and Bone Morphogenetic Protein 2 on Odonto/Osteogenic Differentiation of Human Dental Pulp Stem Cells In Vitro”. The Journal of Endodontics 6 (2017): 930-935.
  42. Bakopoulou A., et al. “Dental pulp stem cells in chitosan/gelatin scaffolds for enhanced orofacial bone regeneration”. Dental Materials: Official Publication of the Academy of Dental Materials 2 (2019): 310-327.
  43. Chakka LRJ., et al. “Application of BMP-2/FGF-2 gene-activated scaffolds for dental pulp capping”. Clinical Oral Investigations 12 (2020): 4427-4437.
  44. Umemura N., et al. “Hyaluronan induces odontoblastic differentiation of dental pulp stem cells via CD44”. Stem Cell Research and Therapy 1 (2016): 135.
  45. Lott K., et al. “Administration of Epidermal Growth Factor (EGF) and Basic Fibroblast Growth Factor (bFGF) to Induce Neural Differentiation of Dental Pulp Stem Cells (DPSC) Isolates”. Biomedicines 11 (2023): 255.
  46. Lee H., et al. “Differential Effects of Extracellular Matrix Glycoproteins Fibronectin And Laminin-5 On Dental Pulp Stem Cell Phenotypes and Responsiveness”. Journal of Functional Biomaterials (2023).
  47. Pilbauerova N., et al. “The Effects of Cryogenic Storage on Human Dental Pulp Stem Cells”. International Journal of Molecular Sciences 9 (2021): 4432.
  48. İslam A., et al. “Comparative evaluation of low-level laser therapy on proliferation of long-term cryopreserved human dental pulp cells isolated from deciduous and permanent teeth”. Lasers in Medical Science 2 (2021): 421-427.
  49. Diana R., et al. “Dental pulp stem cells response on the nanotopography of scaffold to regenerate dentin-pulp complex tissue”. Regenerative Therapy 15 (2020): 243-250.

Karl Kingsley., et al. “Dental Pulp Stem Cell Differentiation Potential of BMP-2 and BMP-4”.”. EC Dental Science 22.3 (2023): 64-76.