Skip to main content

Advertisement

SpringerLink
Log in

Effect of Lactoferrin on Odontogenic Differentiation of Stem Cells Derived from Human 3rd Molar Tooth Germ

  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

Abstract

Stem cell technology has been a great hope for the treatment of many common tissue regeneration-related diseases. Therefore, the main challenge in hard tissue engineering is to make a successful combination of stem cells and efficient inductors such as biomaterials or growth factors, in the concept of stem cell conversion into odontogenic cell. Even though lactoferrin has been reported to promote bone growth in vivo, the molecular mechanism of teeth formation has not been elucidated yet. Different concentrations of lactoferrin were prepared for the analysis of cell toxicity and differentiation evaluations. The odontogenic differentiation of human tooth germ stem cells (hTGSCs) was assessed by gene expression analysis, determination of protein levels in odontogenic differentiation-related protein, measuring alkaline phosphatase (ALP) activity, mineralization, and calcium deposit levels. Lactoferrin-treated group showed the highest ALP activity as opposed to the other groups which were untreated. In addition, the gene expression levels as well as the protein levels of odontogenic factors were found to be high in compared to the control groups. In the current study, it is shown for the first time that there is a significant increase in odontogenic differentiation capacity in hTGSCs when lactoferrin is applied in vitro. The study offers a considerable promise for the development of pulp regeneration by using stem cell technology combined with lactoferrin in functional tooth tissue engineering.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Murray, P. E., Garcia-Godoy, F., & Hargreaves, K. M. (2007). Regenerative endodontics: a review of current status and a call for action. Journal of Endodontics, 33, 377–390.

    Article  Google Scholar 

  2. Hermann, B. W. (1952). On the reaction of the dental pulp to vital amputation and calxyl capping. Deutsche zahnärztliche Zeitschrift, 7, 1446–1447.

    CAS  Google Scholar 

  3. Block, M. S., Cervini, D., Chang, A., & Gottsegen, G. B. (1995). Anterior maxillary advancement using tooth-supported distraction osteogenesis. Journal of Oral and Maxillofacial Surgery, 53, 561–565.

    Article  CAS  Google Scholar 

  4. Kassolis, J. D., Rosen, P. S., & Reynolds, M. A. (2000). Alveolar ridge and sinus augmentation utilizing platelet-rich plasma in combination with freeze-dried bone allograft: case series. Journal of Periodontology, 71, 1654–1661.

    Article  CAS  Google Scholar 

  5. Fujimura, K., Bessho, K., Kusumoto, K., Ogawa, Y., & Iizuka, T. (1995). Experimental studies on bone inducing activity of composites of atelopeptide type I collagen as a carrier for ectopic osteoinduction by rhBMP-2. Biochemical and Biophysical Research Communications, 208, 316–322.

    Article  CAS  Google Scholar 

  6. Heijl, L., Heden, G., Svardstrom, G., & Ostgren, A. (1997). Enamel matrix derivative (EMDOGAIN) in the treatment of intrabony periodontal defects. Journal of Clinical Periodontology, 24, 705–714.

    Article  CAS  Google Scholar 

  7. Lin, L., Chen, M. Y., Ricucci, D., & Rosenberg, P. A. (2010). Guided tissue regeneration in periapical surgery. Journal of Endodontics, 36, 618–625.

    Article  Google Scholar 

  8. Takayama, S., Murakami, S., Shimabukuro, Y., Kitamura, M., & Okada, H. (2001). Periodontal regeneration by FGF-2 (bFGF) in primate models. Journal of Dental Research, 80, 2075–2079.

    Article  CAS  Google Scholar 

  9. Linde, A., & Goldberg, M. (1993). Dentinogenesis. Critical Reviews in Oral Biology and Medicine, 4, 679–728.

    CAS  Google Scholar 

  10. Yalvac, M. E., Yilmaz, A., Mercan, D., Aydin, S., Dogan, A., Arslan, A., Demir, Z., Salafutdinov, I. I., Shafigullina, A. K., Sahin, F., Rizvanov, A. A., & Palotas, A. (2011). Differentiation and neuro-protective properties of immortalized human tooth germ stem cells. Neurochemical Research, 36, 2227–2235.

    Article  CAS  Google Scholar 

  11. Tasli, P. N., Yalvac, M. E., Sofiev, N., & Sahin, F. (2013). Effect of F68, F127, and P85 pluronic block copolymers on odontogenic differentiation of human tooth germ stem cells. Journal of Endodontics, 39, 1265–1271.

    Article  Google Scholar 

  12. Tasli, P. N., Tapsin, S., Demirel, S., Yalvac, M. E., Akyuz, S., Yarat, A., & Sahin, F. (2013). Isolation and characterization of dental pulp stem cells from a patient with Papillon-Lefevre syndrome. Journal of Endodontics, 39, 31–38.

    Article  Google Scholar 

  13. Dogan, A., Yalvac, M. E., Sahin, F., Kabanov, A. V., Palotas, A., & Rizvanov, A. A. (2012). Differentiation of human stem cells is promoted by amphiphilic pluronic block copolymers. International Journal of Nanomedicine, 7, 4849–4860.

    CAS  Google Scholar 

  14. Tasli, P. N., Aydin, S., Yalvac, M. E., & Sahin, F. (2014). Bmp 2 and Bmp 7 induce odonto- and osteogenesis of human tooth germ stem cells. Applied Biochemistry and Biotechnology, 173, 3016–3025.

    Article  Google Scholar 

  15. Tasli, P. N., Dogan, A., Demirci, S., & Sahin, F. (2013). Boron enhances odontogenic and osteogenic differentiation of human tooth germ stem cells (hTGSCs) in vitro. Biological Trace Element Research, 153, 419–427.

    Article  CAS  Google Scholar 

  16. Metz-Boutigue, M. H., Jolles, J., Mazurier, J., Schoentgen, F., Legrand, D., Spik, G., Montreuil, J., & Jolles, P. (1984). Human lactotransferrin: amino acid sequence and structural comparisons with other transferrins. European Journal of Biochemistry, 145, 659–676.

    Article  CAS  Google Scholar 

  17. Lonnerdal, B., & Iyer, S. (1995). Lactoferrin: molecular structure and biological function. Annual Review of Nutrition, 15, 93–110.

    Article  CAS  Google Scholar 

  18. Nagasawa, T., Kiyosawa, I., & Kuwahara, K. (1972). Amounts of lactoferrin in human colostrum and milk. Journal of Dairy Science, 55, 1651–1659.

    Article  CAS  Google Scholar 

  19. Sanchez, L., Aranda, P., Perez, M. D., & Calvo, M. (1988). Concentration of lactoferrin and transferrin throughout lactation in cow’s colostrum and milk. Biological Chemistry Hoppe-Seyler, 369, 1005–1008.

    Article  CAS  Google Scholar 

  20. Cornish, J., Callon, K. E., Naot, D., Palmano, K. P., Banovic, T., Bava, U., Watson, M., Lin, J. M., Tong, P. C., Chen, Q., Chan, V. A., Reid, H. E., Fazzalari, N., Baker, H. M., Baker, E. N., Haggarty, N. W., Grey, A. B., & Reid, I. R. (2004). Lactoferrin is a potent regulator of bone cell activity and increases bone formation in vivo. Endocrinology, 145, 4366–4374.

    Article  CAS  Google Scholar 

  21. Yalvac, M. E., Rizvanov, A. A., Kilic, E., Sahin, F., Mukhamedyarov, M. A., Islamov, R. R., & Palotas, A. (2009). Potential role of dental stem cells in the cellular therapy of cerebral ischemia. Current Pharmaceutical Design, 15, 3908–3916.

    Article  CAS  Google Scholar 

  22. Caccavo, D., Sebastiani, G. D., Di Monaco, C., Guido, F., Galeazzi, M., Ferri, G. M., Bonomo, L., & Afeltra, A. (1999). Increased levels of lactoferrin in synovial fluid but not in serum from patients with rheumatoid arthritis. International Journal of Clinical and Laboratory Research, 29, 30–35.

    Article  CAS  Google Scholar 

  23. Nam, S., Won, J. E., Kim, C. H., & Kim, H. W. (2011). Odontogenic differentiation of human dental pulp stem cells stimulated by the calcium phosphate porous granules. Journal of Tissue Engineering, 2011, 812547.

    Google Scholar 

  24. Zhu, Q., Gibson, M. P., Liu, Q., Liu, Y., Lu, Y., Wang, X., Feng, J. Q., & Qin, C. (2012). Proteolytic processing of dentin sialophosphoprotein (DSPP) is essential to dentinogenesis. Journal of Biological Chemistry, 287, 30426–30435.

    Article  CAS  Google Scholar 

  25. Lisignoli, G., Cristino, S., Piacentini, A., Toneguzzi, S., Grassi, F., Cavallo, C., Zini, N., Solimando, L., Mario Maraldi, N., & Facchini, A. (2005). Cellular and molecular events during chondrogenesis of human mesenchymal stromal cells grown in a three-dimensional hyaluronan based scaffold. Biomaterials, 26, 5677–5686.

    Article  CAS  Google Scholar 

  26. Yagi, M., Suzuki, N., Takayama, T., Arisue, M., Kodama, T., Yoda, Y., Otsuka, K., & Ito, K. (2009). Effects of lactoferrin on the differentiation of pluripotent mesenchymal cells. Cell Biology International, 33, 283–289.

    Article  CAS  Google Scholar 

  27. Terasawa, M., Shimokawa, R., Terashima, T., Ohya, K., Takagi, Y., & Shimokawa, H. (2004). Expression of dentin matrix protein 1 (DMP1) in nonmineralized tissues. Journal of Bone and Mineral Metabolism, 22, 430–438.

    Article  CAS  Google Scholar 

  28. Fukumoto, S., Kiba, T., Hall, B., Iehara, N., Nakamura, T., Longenecker, G., Krebsbach, P. H., Nanci, A., Kulkarni, A. B., & Yamada, Y. (2004). Ameloblastin is a cell adhesion molecule required for maintaining the differentiation state of ameloblasts. Journal of Cell Biology, 167, 973–983.

    Article  CAS  Google Scholar 

  29. Serigano, K., Sakai, D., Hiyama, A., Tamura, F., Tanaka, M., & Mochida, J. (2010). Effect of cell number on mesenchymal stem cell transplantation in a canine disc degeneration model. Journal of Orthopaedic Research, 28, 1267–1275.

    Article  Google Scholar 

  30. Xiao, S., Yu, C., Chou, X., Yuan, W., Wang, Y., Bu, L., Fu, G., Qian, M., Yang, J., Shi, Y., Hu, L., Han, B., Wang, Z., Huang, W., Liu, J., Chen, Z., Zhao, G., & Kong, X. (2001). Dentinogenesis imperfecta 1 with or without progressive hearing loss is associated with distinct mutations in DSPP. Nature Genetics, 27, 201–204.

    Article  CAS  Google Scholar 

  31. Zhang, X., Zhao, J., Li, C., Gao, S., Qiu, C., Liu, P., Wu, G., Qiang, B., Lo, W. H., & Shen, Y. (2001). DSPP mutation in dentinogenesis imperfecta Shields type II. Nature Genetics, 27, 151–152.

    Article  CAS  Google Scholar 

  32. Holappa, H., Nieminen, P., Tolva, L., Lukinmaa, P. L., & Alaluusua, S. (2006). Splicing site mutations in dentin sialophosphoprotein causing dentinogenesis imperfecta type II. European Journal of Oral Sciences, 114, 381–384.

    Article  CAS  Google Scholar 

  33. Sreenath, T., Thyagarajan, T., Hall, B., Longenecker, G., D’Souza, R., Hong, S., Wright, J. T., MacDougall, M., Sauk, J., & Kulkarni, A. B. (2003). Dentin sialophosphoprotein knockout mouse teeth display widened predentin zone and develop defective dentin mineralization similar to human dentinogenesis imperfecta type III. Journal of Biological Chemistry, 278, 24874–24880.

    Article  CAS  Google Scholar 

  34. Owen, T. A., Aronow, M., Shalhoub, V., Barone, L. M., Wilming, L., Tassinari, M. S., Kennedy, M. B., Pockwinse, S., Lian, J. B., & Stein, G. S. (1990). Progressive development of the rat osteoblast phenotype in vitro: reciprocal relationships in expression of genes associated with osteoblast proliferation and differentiation during formation of the bone extracellular matrix. Journal of Cellular Physiology, 143, 420–430.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

We would like to thank Safa Aydın for his help.

Conflict of Interest

The authors deny any conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, 26 Ağustos Campus, Kayisdagi cad., 34755, Kayisdagi, Istanbul, Turkey

    Pakize Neslihan Taşlı & Fikrettin Şahin

Authors
  1. Pakize Neslihan Taşlı
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fikrettin Şahin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fikrettin Şahin.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Taşlı, P.N., Şahin, F. Effect of Lactoferrin on Odontogenic Differentiation of Stem Cells Derived from Human 3rd Molar Tooth Germ. Appl Biochem Biotechnol 174, 2257–2266 (2014). https://doi.org/10.1007/s12010-014-1204-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-014-1204-8

Keywords

Search

Navigation