Abstract
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.
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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.
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.
Chai, Y., and Slavkin, H.C. (2003). Prospects for tooth regeneration in the 21st century: a perspective. Microsc. Res. Tech. 60, 469–479.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Maki, J.M., and Kivirikko, K.I. (2001). Cloning and characterization of a fourth human lysyl oxidase isoenzyme. Biochem. J. 355, 381–387.
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.
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.
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.
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.
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.
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.
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.
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.
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Kim, JH., Lee, EH., Park, Hj. et al. The role of lysyl oxidase-like 2 in the odontogenic differentiation of human dental pulp stem cells. Mol Cells 35, 543–549 (2013). https://doi.org/10.1007/s10059-013-0080-3
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DOI: https://doi.org/10.1007/s10059-013-0080-3