Skip to main content

Advertisement

SpringerLink
Log in

Effects of human full-length amelogenin on the proliferation of human mesenchymal stem cells derived from bone marrow

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Amelogenins are enamel matrix proteins that play a crucial role in enamel formation. Recent studies have revealed that amelogenins also have cell signaling properties. Although amelogenins had been described as specific products of ameloblasts, recent research has demonstrated their expression in bone marrow stromal cells. In this study, we examined the effect of recombinant human full-length amelogenin (rh174) on the proliferation of human mesenchymal stem cells (MSCs) derived from bone marrow and characterized the associated changes in intracellular signaling pathways. MSCs were treated with rh174 ranging in dose from 0 to 1,000 ng/ml. Cell proliferative activity was analyzed by bromodeoxyuridine (BrdU) immunoassay. The expression of lysosomal-associated membrane protein 1 (LAMP1), a possible amelogenin receptor, in MSCs was analyzed. Anti-LAMP1 antibody was used to block the binding of rh174 to LAMP1. The MAPK-ERK pathway was examined by Cellular Activation of Signaling ELISA (CASE) kit and western blot analysis. A specific MAPK inhibitor, U0126, was used to block ERK activity. It was shown that rh174 increased the proliferation of MSCs and MAPK-ERK activity. The MSC proliferation and MAPK-ERK activity enhanced by rh174 were reduced by the addition of anti-LAMP1 antibody. Additionally, the increased proliferation of MSCs induced by rh174 was inhibited in the presence of U0126. In conclusion, it is demonstrated that rh174 increases the proliferation of MSCs by interaction with LAMP1 through the MAPK-ERK signaling pathway, indicating the possibility of MSC application to tissue regeneration in the orofacial region.

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
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Abe K, Miyoshi K, Muto T, Ruspita I, Horiguchi T, Nagata T, Noma T (2007) Establishment and characterization of rat dental epithelial derived ameloblast-lineage clones. J Biosci Bioeng 103:479–485

    Article  CAS  PubMed  Google Scholar 

  • Boabaid F, Gibson CW, Kuehl MA, Berry JE, Snead ML, Nociti FH Jr, Katchburian E, Somerman MJ (2004) Leucine-rich amelogenin peptide: a candidate signaling molecule during cementogenesis. J Periodontol 75:1126–1136

    Article  CAS  PubMed  Google Scholar 

  • Briquet A, Dubois S, Bekaert S, Dolhet M, Beguin Y, Gothot A (2009) Prolonged ex vivo culture of human bone marrow mesenchymal stem cells influences their supportive activity toward NOD/SCID-repopulating cells and committed progenitor cells of B lymphoid and myeloid lineages. Haematologica 95:47–56

    Article  PubMed  Google Scholar 

  • Cook NR, Row PE, Davidson HW (2004) Lysosome associated membrane protein 1 (Lamp1) traffics directly from the TGN to early endosomes. Traffic 5:685–699

    Article  CAS  PubMed  Google Scholar 

  • DenBesten PK, Yan Y, Featherstone JD, Hilton JF, Smith CE, Li W (2002) Effects of fluoride on rat dental enamel matrix proteinases. Arch Oral Biol 47:763–770

    Article  CAS  PubMed  Google Scholar 

  • Fincham AG, Moradian-Oldak J, Simmer JP (1999) The structural biology of the developing dental enamel matrix. J Struct Biol 126:270–299

    Article  CAS  PubMed  Google Scholar 

  • Guida L, Annunziata M, Carinci F, Di Feo A, Passaro I, Oliva A (2007) In vitro biologic response of human bone marrow stromal cells to enamel matrix derivative. J Periodontol 78:2190–2196

    Article  CAS  PubMed  Google Scholar 

  • Hatakeyama J, Philp D, Hatakeyama Y, Haruyama N, Shum L, Aragon MA, Yuan Z, Gibson CW, Sreenath T, Kleinman HK, Kulkarni AB (2006) Amelogenin-mediated regulation of osteoclastogenesis, and periodontal cell proliferation and migration. J Dent Res 85:144–149

    Article  CAS  PubMed  Google Scholar 

  • Hatakeyama J, Sreenath T, Hatakeyama Y, Thyagarajan T, Shum L, Gibson CW, Wright JT, Kulkarni AB (2003) The receptor activator of nuclear factor-kappa B ligand-mediated osteoclastogenic pathway is elevated in amelogenin-null mice. J Biol Chem 278:35743–35748

    Article  CAS  PubMed  Google Scholar 

  • Haze A, Taylor AL, Blumenfeld A, Rosenfeld E, Leiser Y, Dafni L, Shay B, Gruenbaum-Cohen Y, Fermon E, Haegewald S, Bernimoulin JP, Deutsch D (2007) Amelogenin expression in long bone and cartilage cells and in bone marrow progenitor cells. Anat Rec (Hoboken) 290:455–460

    CAS  Google Scholar 

  • Inage T, Shimokawa H, Wakao K, Sasaki S (1996) Gene expression and localization of amelogenin in the rat incisor. Adv Dent Res 10:201–207

    Article  CAS  PubMed  Google Scholar 

  • Kim EK, Choi EJ (2010) Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta 1802:396–405

    CAS  PubMed  Google Scholar 

  • Li W, Gao C, Yan Y, DenBesten P (2003) X-linked amelogenesis imperfecta may result from decreased formation of tyrosine rich amelogenin peptide (TRAP). Arch Oral Biol 48:177–183

    Article  CAS  PubMed  Google Scholar 

  • Li X, Shu R, Liu D, Jiang S (2010) Different effects of 25-kDa amelogenin on the proliferation, attachment and migration of various periodontal cells. Biochem Biophys Res Commun 394:581–586

    Article  CAS  PubMed  Google Scholar 

  • Matsuda N, Horikawa M, Watanabe M, Kitagawa S, Kudo Y, Takata T (2002) Possible involvement of extracellular signal-regulated kinases 1/2 in mitogenic response of periodontal ligament cells to enamel matrix derivative. Eur J Oral Sci 110:439–444

    Article  CAS  PubMed  Google Scholar 

  • Mii S, Khalil RA, Morgan KG, Ware JA, Kent KC (1996) Mitogen-activated protein kinase and proliferation of human vascular smooth muscle cells. Am J Physiol 270:142–150

    Google Scholar 

  • Moradian-Oldak J, Simmer JP, Sarte PE, Zeichner-David M, Fincham AG (1994) Specific cleavage of a recombinant murine amelogenin at the carboxy-terminal region by a proteinase fraction isolated from developing bovine tooth enamel. Arch Oral Biol 39:647–656

    Article  CAS  PubMed  Google Scholar 

  • Nebgen DR, Inoue H, Sabsay B, Wei K, Ho CS, Veis A (1999) Identification of the chondrogenic-inducing activity from bovine dentin (bCIA) as a low-molecular-mass amelogenin polypeptide. J Dent Res 78:1484–1494

    Article  CAS  PubMed  Google Scholar 

  • Neuhuber B, Swanger SA, Howard L, Mackay A, Fischer I (2008) Effects of plating density and culture time on bone marrow stromal cell characteristics. Exp Hematol 36:1176–1185

    Article  PubMed  Google Scholar 

  • Ryu OH, Fincham AG, Hu CC, Zhang C, Qian Q, Bartlett JD, Simmer JP (1999) Characterization of recombinant pig enamelysin activity and cleavage of recombinant pig and mouse amelogenins. J Dent Res 78:743–750

    Article  CAS  PubMed  Google Scholar 

  • Sasaki S, Shimokawa H (1995) The amelogenin gene. Int J Dev Biol 39:127–133

    CAS  PubMed  Google Scholar 

  • Tanabe T, Fukae M, Uchida T, Shimizu M (1992) The localization and characterization of proteinases for the initial cleavage of porcine amelogenin. Calcif Tissue Int 51:213–217

    Article  CAS  PubMed  Google Scholar 

  • Tompkins K, George A, Veis A (2006) Characterization of a mouse amelogenin [A-4]/M59 cell surface receptor. Bone 38:172–180

    Article  CAS  PubMed  Google Scholar 

  • Tsutsumi S, Shimazu A, Miyazaki K, Pan H, Koike C, Yoshida E, Takagishi K, Kato Y (2001) Retention of multilineage differentiation potential of mesenchymal cells during proliferation in response to FGF. Biochem Biophys Res Commun 288:413–419

    Article  CAS  PubMed  Google Scholar 

  • Veis A (2003) Amelogenin gene splice products: potential signaling molecules. Cell Mol Life Sci 60:38–55

    Article  CAS  PubMed  Google Scholar 

  • Veis A, Tompkins K, Alvares K, Wei K, Wang L, Wang XS, Brownell AG, Jengh SM, Healy KE (2000) Specific amelogenin gene splice products have signaling effects on cells in culture and in implants in vivo. J Biol Chem 275:41263–41272

    Article  CAS  PubMed  Google Scholar 

  • Viswanathan HL, Berry JE, Foster BL, Gibson CW, Li Y, Kulkarni AB, Snead ML, Somerman MJ (2003) Amelogenin: a potential regulator of cementum-associated genes. J Periodontol 74:1423–1431

    Article  CAS  PubMed  Google Scholar 

  • Wakida K, Amizuka N, Murakami C, Satoda T, Fukae M, Simmer JP, Ozawa H, Uchida T (1999) Maturation ameloblasts of the porcine tooth germ do not express amelogenin. Histochem Cell Biol 111:297–303

    Article  CAS  PubMed  Google Scholar 

  • Warotayanont R, Zhu D, Snead ML, Zhou Y (2008) Leucine-rich amelogenin peptide induces osteogenesis in mouse embryonic stem cells. Biochem Biophys Res Commun 367:1–6

    Google Scholar 

  • Weissman IL (2000) Stem cells: units of development, units of regeneration, and units in evolution. Cell 100:157–168

    Article  CAS  PubMed  Google Scholar 

  • Yang J, Wu H, Hu N, Gu X, Ding F (2009) Effects of bone marrow stromal cell-conditioned medium on primary cultures of peripheral nerve tissues and cells. Neurochem Res 34:1685–1694

    Article  CAS  PubMed  Google Scholar 

  • Zeldich E, Koren R, Nemcovsky C, Weinreb M (2007) Enamel matrix derivative stimulates human gingival fibroblast proliferation via ERK. J Dent Res 86:41–46

    Article  CAS  PubMed  Google Scholar 

  • Zhang H, Tompkins K, Garrigues J, Snead ML, Gibson CW, Somerman MJ (2010) Full length amelogenin binds to cell surface LAMP-1 on tooth root/periodontium associated cells. Arch Oral Biol 55:417–425

    Article  CAS  PubMed  Google Scholar 

  • Zou Y, Wang H, Shapiro JL, Okamoto CT, Brookes SJ, Lyngstadaas SP, Snead ML, Paine ML (2007) Determination of protein regions responsible for interactions of amelogenin with CD63 and LAMP1. Biochem J 408:347–354

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Drs. Pamela DenBesten and Wu Li, Department of Orofacial Sciences, University of California, San Francisco, for kindly providing valuable technical support, advice, vector, and antibody for rh174. This research was supported by Grant-in-Aid (No. 20390522) for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

Author information

Authors and Affiliations

  1. Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan

    Yu-Ching Huang, Kotaro Tanimoto, Yuki Tanne, Takashi Kamiya, Ryo Kunimatsu, Masahiko Michida, Motoko Yoshioka, Yuki Yoshimi & Kazuo Tanne

  2. Department of Dental and Medical Biochemistry, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8553, Japan

    Yukio Kato

Authors
  1. Yu-Ching Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kotaro Tanimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yuki Tanne
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takashi Kamiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ryo Kunimatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Masahiko Michida
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Motoko Yoshioka
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yuki Yoshimi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yukio Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Kazuo Tanne
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kotaro Tanimoto.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huang, YC., Tanimoto, K., Tanne, Y. et al. Effects of human full-length amelogenin on the proliferation of human mesenchymal stem cells derived from bone marrow. Cell Tissue Res 342, 205–212 (2010). https://doi.org/10.1007/s00441-010-1064-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-010-1064-7

Keywords

Search

Navigation