Basic Research| Volume 38, ISSUE 6, P769-773, June 2012

Lysyl Oxidase and the Lysyl Oxidase–like Protein Modulate Odontoblastic Differentiation of Human Dental Pulp Cells

Published:April 23, 2012DOI:



      The lysyl oxidase (LOX) family is an emerging family of amine oxidases responsible for the formation of collagen fibrils in the extracellular matrix. To date, 5 LOX family genes have been identified in humans, encoding LOX and LOX-like proteins (LOXL, LOXL2, LOXL3, and LOXL4). The goal of this study was to evaluate the expression and function of the LOX family genes in odontoblastic differentiation of human dental pulp (HDP) cells.


      Expression of the LOX family genes was assessed by reverse transcriptase polymerase chain reaction analysis, and the amine oxidase activity of HDP cells was evaluated by peroxidase-coupled fluorometric assays. Mineral nodule formation and expression of odontoblastic marker genes were assessed in the presence and absence of specific small interfering RNAs (siRNAs) of the LOX family genes.


      Among the LOX family genes, only LOX and LOXL showed prominent expression during odontoblastic differentiation of HDP cells. Suppression of LOX and LOXL expression by siRNA-induced interference substantially decreased the amine oxidase activity of the differentiating HDP cells. Furthermore, interference of LOX and LOXL expression inhibited mineral nodule formation and expression of odontoblastic marker genes during odontoblastic differentiation of HDP cells.


      These findings show for the first time that the LOX- and LOXL-mediated organization of collagen fibrils in extracellular matrices of HDP cells might be an important regulator for odontoblastic differentiation of HDP cells.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Endodontics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Kagan H.M.
        • Trackman P.C.
        Properties and function of lysyl oxidase.
        Am J Respir Cell Mol Biol. 1991; 5: 206-210
        • Kim Y.
        • Boyd C.D.
        • Csiszar K.
        A new gene with sequence and structural similarity to the gene encoding human lysyl oxidase.
        J Biol Chem. 1995; 270: 7176-7182
        • Saito H.
        • Papaconstantinou J.
        • Sato H.
        • Goldstein S.
        Regulation of a novel gene encoding a lysyl oxidase-related protein in cellular adhesion and senescence.
        J Biol Chem. 1997; 272: 8157-8160
        • Jourdan-Le Saux C.
        • Tomsche A.
        • Ujfalusi A.
        • Jia L.
        • Csiszar K.
        Central nervous system, uterus, heart, and leukocyte expression of the LOXL3 gene, encoding a novel lysyl oxidase-like protein.
        Genomics. 2001; 74: 211-218
        • Asuncion L.
        • Fogelgren B.
        • Fong K.S.
        • et al.
        A novel human lysyl oxidase-like gene (LOXL4) on chromosome 10q24 has an altered scavenger receptor cysteine rich domain.
        Matrix Biol. 2004; 20: 487-491
        • Jung S.T.
        • Kim M.S.
        • Seo J.Y.
        • Kim H.C.
        • Kim Y.
        Purification of enzymatically active human lysyl oxidase (LOX) and lysyl oxidase-like protein (LOXL) from Escherichia coli inclusion bodies.
        Protein Expr Purifi. 2003; 31: 240-246
        • Kim M.S.
        • Kim S.S.
        • Jung S.T.
        • et al.
        Expression and purification of enzymatically active forms of the human lysyl oxidase-like protein 4.
        J Biol Chem. 2003; 278: 52071-52074
        • Lee J.E.
        • Kim Y.
        Tissue-specific variant of the human lysyl oxidase-like protein 3 (LOXL3) functions as an amine oxidase with substrate specificity.
        J Biol Chem. 2006; 281: 37282-37290
        • Kim Y.M.
        • Kim E.C.
        • Kim Y.
        The human lysyl oxidase-like 2 protein functions as an amine oxidase toward collagen and elastin.
        Mol Biol Rep. 2011; 38: 145-149
        • Domenicucci C.
        • Goldberg H.A.
        • Sodek J.
        Identification of lysyl oxidase and TRAMP as the major proteins in dissociative extracts of the demineralized collagen matrix of porcine dentine.
        Connect Tissue Res. 1997; 36: 151-163
        • Min K.S.
        • Kwon Y.Y.
        • Lee H.J.
        • et al.
        Effects of proinflammatory cytokines on the expression of mineralization markers and heme oxygenase-1 in human pulp cells.
        J Endod. 2006; 32: 39-43
        • Wei X.
        • Ling J.
        • Wu L.
        • Liu L.
        • Xiao Y.
        Expression of mineralization markers in dental pulp cells.
        J Endod. 2007; 33: 703-708
        • Min K.S.
        • Lee Y.M.
        • Hong S.O.
        • Kim E.C.
        Simvastatin promotes odontoblastic differentiation and expression of angiogenic factors via heme oxygenase-1 in primary cultured human dental pulp cells.
        J Endod. 2010; 36: 447-452
        • Palamakumbura A.H.
        • Trackman P.C.
        A fluorometric assay for detection of lysyl oxidase enzyme activity in biological samples.
        Anal Biochem. 2002; 300: 245-251
        • Chen S.
        • Rani S.
        • Wu Y.
        • et al.
        Differential regulation of dentin sialophosphoprotein expression by Runx2 during odontoblast cytodifferentiation.
        J Biol Chem. 2005; 280: 29717-29727
        • Hannon G.J.
        • Rossi J.J.
        Unlocking the potential of the human genome with RNA interference.
        Nature. 2004; 431: 371-378
        • Linde A.
        • Goldberg M.
        Crit Rev Oral Biol Med. 1993; 4: 679-728
        • Kim J.K.
        • Baker J.
        • Nor J.E.
        • Hill E.E.
        mTor plays an important role in odontoblast differentiation.
        J Endod. 2011; 37: 1081-1085
        • Zhao Z.
        • Liu H.
        • Wang D.
        ADAM28 manipulates proliferation, differentiation, and apoptosis of human dental pulp stem cells.
        J Endod. 2011; 37: 332-339
        • Okamoto Y.
        • Sonoyama W.
        • Ono M.
        • et al.
        Simvastatin induces the odontogenic differentiation of human dental pulp stem cells in vitro and in vivo.
        J Endod. 2009; 35: 367-372
        • Butler W.T.
        • Ritchie H.
        The nature and functional significance of dentin extracellular matrix proteins.
        Int J Dev Biol. 1995; 39: 169-179
        • Ruch J.V.
        Odontoblast commitment and differentiation.
        Biochem Cell Biol. 1998; 76: 923-938
        • Nakao K.
        • Itoh M.
        • Tomita Y.
        • Tomooka Y.
        • Tsuji T.
        FGF-2 potently induces both proliferation and DSP expression in collagen type I gel cultures of adult incisor immature pulp cell.
        Biochem Biophys Res Commun. 2004; 325: 1052-1059
        • Harris H.
        The human alkaline phosphatases: what we know and what we don't know.
        Clin Chim Acta. 1989; 186: 133-150
        • Butler W.T.
        • Brunn J.C.
        • Qin C.
        Dentin extracellular matrix (ECM) proteins: comparison to bone ECM and contribution to dynamics of dentinogenesis.
        Connect Tissue Res. 2003; 44: 171-178
        • Yamakoshi Y.
        Dentinogenesis and dentin sialophosphoprotein (DSPP).
        J Oral Biosci. 2009; 51: 134