title: Amelogenins: Multi-Functional Enamel Matrix Proteins and Their Binding Partners.
abstract: Amelogenins are the most abundant extracellular matrix proteins secreted by ameloblasts during tooth development and are important for enamel formation. Recently, amelogenins have been detected not only in ameloblasts, which are differentiated from the epithelial cell lineage, but also in other tissues, including mesenchymal tissues at low levels, suggesting that amelogenins possess other functions in these tissues. The therapeutic application of an enamel matrix derivative rich in amelogenins resulted in the regeneration of cementum, alveolar bone, and periodontal ligament (PDL) in the treatment of experimental or human periodontitis, indicating the attractive potential of amelogenin in hard tissue formation. In addition, a full-length amelogenin (M180) and leucine-rich amelogenin peptide (LRAP) regulate cementoblast/PDL cell proliferation and migrationin vitro. Interestingly, amelogenin null mice show increased osteoclastogenesis and root resorption in periodontal tissues. Recombinant amelogenin proteins suppress osteoclastogenesisin vivoandin vitro, suggesting that amelogenin is involved in preventing idiopathic root resorption. Amelogenins are implicated in tissue-specific epithelial-mesenchymal or mesenchymal-mesenchymal signaling; however, the precise molecular mechanism has not been characterized. In this review, we first discuss the emerging evidence for the additional roles of M180 and LRAP as signaling molecules in mesenchymal cells. Next, we show the results of a yeast two-hybrid assay aimed at identifying protein-binding partners for LRAP. We believe that gaining further insights into the signaling pathway modulated by the multifunctional amelogenin proteins will lead to the development of new therapeutic approaches for treating dental diseases and disorders.
authors.affiliation: GCOE Program, International Research Center for Molecular Science in Tooth and Bone Diseases Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan ; Maxillofacial Orthognathics, Department of Maxillofacial Reconstruction and Function Division of Maxillofacial/Neck Reconstruction, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Haruyama
authors.forename: Junko
authors.initials: J
authors.lastname: Hatakeyama
authors.forename: Keiji
authors.initials: K
authors.lastname: Moriyama
authors.forename: Ashok B
authors.initials: AB
authors.lastname: Kulkarni
keywords: M180; amelogenin; leucine-rich amelogenin peptide(LRAP); signaling molecules; yeast two-hybrid
references.citation: Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000 Aug;90(2):218-23
references.pmid: 10936841
references.citation: J Biol Chem. 1999 Jan 1;274(1):335-44
references.pmid: 9867848
references.citation: Exp Cell Res. 1999 Nov 1;252(2):243-9
references.pmid: 11501563
references.citation: Biochem Biophys Res Commun. 2009 Sep 25;387(3):558-63
references.pmid: 19615979
references.citation: J Struct Biol. 2011 Feb;173(2):250-60
references.pmid: 21074619
references.citation: Biochim Biophys Acta. 1989 Apr 25;991(1):12-8
references.pmid: 2469482
references.citation: J Dent Res. 1997 Feb;76(2):641-7
references.pmid: 9062557
references.citation: J Dent Res. 2007 Jul;86(7):594-9
references.pmid: 17586703
references.citation: Arch Oral Biol. 2007 Mar;52(3):237-43
references.pmid: 17101114
references.citation: Lung Cancer. 2008 Jun;60(3):309-12
references.pmid: 18462829
references.citation: Trends Biochem Sci. 2002 Jul;27(7):329-32
references.pmid: 12114016
references.citation: J Biol Chem. 1999 Jan 22;274(4):2464-71
references.pmid: 9891017
references.citation: Cell Tissue Res. 2010 Nov;342(2):205-12
references.pmid: 20967466
references.citation: J Immunol. 2008 Oct 1;181(7):4742-51
references.pmid: 18802077
references.citation: J Clin Periodontol. 1997 Sep;24(9 Pt 2):685-92
references.pmid: 9310873
references.citation: Ciba Found Symp. 1997;205:246-55; discussion 255-60
references.pmid: 9189629
references.citation: J Dent Res. 2006 Feb;85(2):144-9
references.pmid: 16434732
references.citation: J Biol Chem. 2001 Sep 28;276(39):36586-97
references.pmid: 11425863
references.citation: Am J Hum Genet. 1992 Feb;50(2):303-16
references.pmid: 1734713
references.citation: J Biol Chem. 2003 Sep 12;278(37):35743-8
references.pmid: 12851394
references.citation: Differentiation. 2009 Sep-Oct;78(2-3):108-15
references.pmid: 19541402
references.citation: Connect Tissue Res. 2002;43(2-3):441-9
references.pmid: 12489196
references.citation: J Biol Chem. 2001 Aug 24;276(34):31871-5
references.pmid: 11406633
references.citation: Cell Mol Life Sci. 2006 Oct;63(19-20):2304-16
references.pmid: 16909208
references.citation: Arch Oral Biol. 1991;36(4):305-17
references.pmid: 2064551
references.citation: Genomics. 1989 Feb;4(2):162-8
references.pmid: 2737677
references.citation: J Biol Chem. 2010 Mar 5;285(10):7384-93
references.pmid: 20048148
references.citation: J Periodontol. 2002 May;73(5):501-4
references.pmid: 12027251
references.citation: J Dent Res. 1999 Sep;78(9):1484-94
references.pmid: 10512382
references.citation: J Biol Chem. 2008 May 30;283(22):15056-62
references.pmid: 18390542
references.citation: Cell Mol Life Sci. 2003 Jan;60(1):38-55
references.pmid: 12613657
references.citation: J Periodontol. 2002 Apr;73(4):433-40
references.pmid: 11990445
references.citation: J Biol Chem. 1980 Oct 25;255(20):9760-8
references.pmid: 7430099
references.citation: Bone. 2006 Feb;38(2):172-80
references.pmid: 16214432
references.citation: J Periodontal Res. 2009 Jun;44(3):289-96
references.pmid: 19462488
references.citation: Curr Opin Cell Biol. 1997 Oct;9(5):616-26
references.pmid: 9330864
references.citation: Biotechnol J. 2008 Dec;3(12):1548-54
references.pmid: 19072909
references.citation: J Bone Miner Res. 2005 Jun;20(6):1032-40
references.pmid: 15883644
references.citation: J Clin Periodontol. 1997 Sep;24(9 Pt 2):669-77
references.pmid: 9310871
references.citation: Arch Oral Biol. 1998 Jun;43(6):497-504
references.pmid: 9717587
references.citation: Biol Chem. 2008 Jun;389(6):695-700
references.pmid: 18627287
references.citation: J Biol Chem. 2005 Jul 1;280(26):24690-7
references.pmid: 15843371
references.citation: Biochem J. 2007 Dec 15;408(3):347-54
references.pmid: 17708745
references.citation: J Biol Chem. 2000 Dec 15;275(50):39654-61
references.pmid: 10980199
references.citation: Biochem J. 1983 Apr 1;211(1):149-54
references.pmid: 6870818
references.citation: Crit Rev Oral Biol Med. 1999;10(4):425-41
references.pmid: 10634581
references.citation: Nature. 2004 Apr 15;428(6984):758-63
references.pmid: 15085135
references.citation: J Dent Res. 2006 Oct;85(10):894-9
references.pmid: 16998127
references.citation: J Neurosci. 2008 Jun 4;28(23):6030-6
references.pmid: 18524908
references.citation: Eur J Oral Sci. 2006 May;114 Suppl 1:190-3; discussion 201-2, 381
references.pmid: 16674684
references.citation: J Mol Evol. 2005 Jan;60(1):12-30
references.pmid: 15696365
references.citation: J Biomed Mater Res A. 2006 Dec 15;79(4):1015-22
references.pmid: 17001657
references.citation: J Biol Chem. 2000 Dec 29;275(52):41263-72
references.pmid: 10998415
references.citation: J Cell Biochem. 2003 Jan 1;88(1):152-64
references.pmid: 12461785
references.citation: J Dent Res. 2009 Feb;88(2):176-81
references.pmid: 19278991
references.citation: Cell Mol Life Sci. 2007 Jan;64(2):244-56
references.pmid: 17187173