Molecules and Cells

, Volume 35, Issue 6, pp 543–549 | Cite as

The role of lysyl oxidase-like 2 in the odontogenic differentiation of human dental pulp stem cells

  • Joo-Hyun Kim
  • Eun-Hyang Lee
  • Hye-jeong Park
  • Eui-Kyun Park
  • Tae-Geon Kwon
  • Hong-In Shin
  • Je-Yoel ChoEmail author
Research Article


Adult human dental pulp stem cells (hDPSCs) are a unique population of precursor cells those are isolated from postnatal dental pulp and have the ability to differentiate into a variety of cell types utilized for the formation of a reparative dentin-like complex. Using LC-MS/MS proteomics approaches, we identified the proteins secreted from the differentiating hDPSCs in mineralization media. Lysyl oxidase-like 2 (LOXL2) was identified as a protein that was down-regulated in the hDPSCs that differentiate into odontoblast-like cells. The role of LOXL2 has not been studied in dental pulp stem cells. LOXL2 mRNA levels were reduced in differentiating hDPSCs, whereas the levels of other LOX family members including LOX, LOXL1, LOXL3, and LOXL4, are increased. The protein expression and secretion levels of LOXL2 were also decreased during odontogenic differentiation. Recombinant LOXL2 protein treatment to hDPSCs resulted in a dose-dependent decrease in the early differentiation and the mineralization accompanying with the lower levels of odontogenic markers such as DSPP, DMP-1 and ALP. These results suggest that LOXL2 has a negative effect on the differentiation of hDPSCs and blocking LOXL2 can promote the hDPSC differentiation to odontoblasts.


human dental pulp stem cells lysyl oxidase-like 2 odontogenic differentiation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Atsawasuwan, P., Mochida, Y., Parisuthiman, D., and Yamauchi, M. (2005). Expression of lysyl oxidase isoforms in MC3T3-E1 osteoblastic cells. Biochem. Biophys. Res. Commun. 327, 1042–1046.PubMedCrossRefGoogle Scholar
  2. Bignon, M., Pichol-Thievend, C., Hardouin, J., Malbouyres, M., Brechot, N., Nasciutti, L., Barret, A., Teillon, J., Guillon, E., Etienne, E., et al. (2011). Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV collagen assembly in the endothelial basement membrane. Blood 118, 3979–3989.PubMedCrossRefGoogle Scholar
  3. Chai, Y., and Slavkin, H.C. (2003). Prospects for tooth regeneration in the 21st century: a perspective. Microsc. Res. Tech. 60, 469–479.PubMedCrossRefGoogle Scholar
  4. d’Aquino, R., Graziano, A., Sampaolesi, M., Laino, G., Pirozzi, G., De Rosa, A., and Papaccio, G. (2007). Human postnatal dental pulp cells co-differentiate into osteoblasts and endotheliocytes: a pivotal synergy leading to adult bone tissue formation. Cell Death Differ. 14, 1162–1171.PubMedCrossRefGoogle Scholar
  5. Duailibi, M.T., Duailibi, S.E., Young, C.S., Bartlett, J.D., Vacanti, J.P., and Yelick, P.C. (2004). Bioengineered teeth from cultured rat tooth bud cells. J. Dent. Res. 83, 523–528.PubMedCrossRefGoogle Scholar
  6. Gronthos, S., Mankani, M., Brahim, J., Robey, P.G., and Shi, S. (2000). Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc. Natl. Acad. Sci. USA 97, 13625–13630.PubMedCrossRefGoogle Scholar
  7. Hayashi, K., Cao, T., Passmore, H., Jourdan-Le Saux, C., Fogelgren, B., Khan, S., Hornstra, I., Kim, Y., Hayashi, M., and Csiszar, K. (2004a). Progressive hair loss and myocardial degeneration in rough coat mice: reduced lysyl oxidase-like (LOXL) in the skin and heart. J. Invest Dermatol. 123, 864–871.PubMedCrossRefGoogle Scholar
  8. Hayashi, K., Fong, K.S., Mercier, F., Boyd, C.D., Csiszar, K., and Hayashi, M. (2004b). Comparative immunocytochemical localization of lysyl oxidase (LOX) and the lysyl oxidase-like (LOXL) proteins: changes in the expression of LOXL during development and growth of mouse tissues. J. Mol. Histol. 35, 845–855.PubMedCrossRefGoogle Scholar
  9. Heo, S.H., Choi, Y.J., Lee, J.H., Lee, J.M., and Cho, J.Y. (2011). S100A2 level changes are related to human periodontitis. Mol. Cells 32, 445–450.PubMedCrossRefGoogle Scholar
  10. Jourdan-Le Saux, C., Tronecker, H., Bogic, L., Bryant-Greenwood, G.D., Boyd, C.D., and Csiszar, K. (1999). The LOXL2 gene encodes a new lysyl oxidase-like protein and is expressed at high levels in reproductive tissues. J. Biol. Chem. 274, 12939–12944.PubMedCrossRefGoogle Scholar
  11. Kagan, H.M., Reddy, V.B., Narasimhan, N., and Csiszar, K. (1995). Catalytic properties and structural components of lysyl oxidase. Ciba Found. Symp. 192, 100–115; discussion 115–121.PubMedGoogle Scholar
  12. Kaku, M., Mochida, Y., Atsawasuwan, P., Parisuthiman, D., and Yamauchi, M. (2007). Post-translational modifications of collagen upon BMP-induced osteoblast differentiation. Biochem. Biophys. Res. Commun. 359, 463–468.PubMedCrossRefGoogle Scholar
  13. Kim, Y.M., Kim, E.C., and Kim, Y. (2011). The human lysyl oxidase-like 2 protein functions as an amine oxidase toward collagen and elastin. Mol. Biol. Rep. 38, 145–149.PubMedCrossRefGoogle Scholar
  14. Koyama, N., Okubo, Y., Nakao, K., and Bessho, K. (2009). Evaluation of pluripotency in human dental pulp cells. J. Oral Maxillofac. Surg. 67, 501–506.PubMedCrossRefGoogle Scholar
  15. Lee, E.H., Park, H.J., Jeong, J.H., Kim, Y.J., Cha, D.W., Kwon, D.K., Lee, S.H., and Cho, J.Y. (2010). The role of asporin in mineralization of human dental pulp stem cells. J. Cell. Physiol. 226, 1676–1682.CrossRefGoogle Scholar
  16. Maki, J.M., and Kivirikko, K.I. (2001). Cloning and characterization of a fourth human lysyl oxidase isoenzyme. Biochem. J. 355, 381–387.PubMedCrossRefGoogle Scholar
  17. Monticone, M., Liu, Y., Tonachini, L., Mastrogiacomo, M., Parodi, S., Quarto, R., Cancedda, R., and Castagnola, P. (2004). Gene expression profile of human bone marrow stromal cells determined by restriction fragment differential display analysis. J. Cell. Biochem. 92, 733–744.PubMedCrossRefGoogle Scholar
  18. Morsczeck, C., Schmalz, G., Reichert, T.E., Vollner, F., Galler, K., and Driemel, O. (2008). Somatic stem cells for regenerative dentistry. Clin. Oral Invest. 12, 113–118.CrossRefGoogle Scholar
  19. Narayanasamy, A., Ahn, J.M., Sung, H.J., Kong, D.H., Ha, K.S., Lee, S.Y., and Cho, J.Y. (2011). Fucosylated glycoproteomic approach to identify a complement component 9 associated with squamous cell lung cancer (SQLC). J. Proteomics 74, 2948–2958.PubMedCrossRefGoogle Scholar
  20. Rodriguez, C., Martinez-Gonzalez, J., Raposo, B., Alcudia, J.F., Guadall, A., and Badimon, L. (2008). Regulation of lysyl oxidase in vascular cells: lysyl oxidase as a new player in cardiovascular diseases. Cardiovasc. Res. 79, 7–13.PubMedCrossRefGoogle Scholar
  21. Saito, H., Papaconstantinou, J., Sato, H., and Goldstein, S. (1997). Regulation of a novel gene encoding a lysyl oxidase-related protein in cellular adhesion and senescence. J. Biol. Chem. 272, 8157–8160.PubMedCrossRefGoogle Scholar
  22. Tretter, V., Altmann, F., and Marz, L. (1991). Peptide-N4-(N-acetylbeta-glucosaminyl)asparagine amidase F cannot release glycans with fucose attached alpha 1–3 to the asparagine-linked Nacetylglucosamine residue. Eur. J. Biochem. 199, 647–652.PubMedCrossRefGoogle Scholar
  23. Yokose, S., Kadokura, H., Tajima, Y., Fujieda, K., Katayama, I., Matsuoka, T., and Katayama, T. (2000). Establishment and characterization of a culture system for enzymatically released rat dental pulp cells. Calcif. Tissue Int. 66, 139–144.PubMedCrossRefGoogle Scholar
  24. Yu, J., He, H., Tang, C., Zhang, G., Li, Y., Wang, R., Shi, J., and Jin, Y. (2010). Differentiation potential of STRO-1+ dental pulp stem cells changes during cell passaging. BMC Cell Biol. 11, 32.PubMedCrossRefGoogle Scholar

Copyright information

© The Korean Society for Molecular and Cellular Biology and Springer Netherlands 2013

Authors and Affiliations

  • Joo-Hyun Kim
    • 1
    • 2
  • Eun-Hyang Lee
    • 3
  • Hye-jeong Park
    • 1
  • Eui-Kyun Park
    • 2
  • Tae-Geon Kwon
    • 4
  • Hong-In Shin
    • 2
  • Je-Yoel Cho
    • 1
    Email author
  1. 1.Department of Veterinary Biochemistry, Brain Korea 21 and Research Institute for Veterinary Science, College of Veterinary MedicineSeoul National UniversitySeoulKorea
  2. 2.Department of Pathology, School of DentistryKyungpook National UniversityDaeguKorea
  3. 3.ProtAnBio, Co.SeoulKorea
  4. 4.Department of Oral and Maxillofacial Surgery, School of DentistryKyungpook National UniversityDaeguKorea

Personalised recommendations