Advertisement

Histochemistry and Cell Biology

, Volume 133, Issue 5, pp 577–584 | Cite as

Possible involvement of melatonin in tooth development: expression of melatonin 1a receptor in human and mouse tooth germs

  • Shuku Kumasaka
  • Masashi Shimozuma
  • Tadafumi Kawamoto
  • Kenji Mishima
  • Reiko Tokuyama
  • Yoko Kamiya
  • Purevsuren Davaadorj
  • Ichiro Saito
  • Kazuhito Satomura
Original Paper

Abstract

Melatonin is known to regulate a variety of physiological processes including control of circadian rhythms, regulation of seasonal reproductive function, regulation of body temperature, free radical scavenging, and so forth. Accumulating evidence from in vitro and in vivo experiments has also suggested that melatonin may have an influence on skeletal growth and bone formation. However, little is known about the effects of melatonin on tooth development and growth, which thus remain to be elucidated. This study was performed to examine the possibility that melatonin might exert its influence on tooth development as well as skeletal growth. Immunohistochemical analysis revealed that melatonin 1a receptor (Mel1aR) was expressed in secretory ameloblasts, the cells of the stratum intermedium and stellate reticulum, external dental epithelial cells, odontoblasts, and dental sac cells. Reverse transcription-polymerase chain reaction and Western blot analysis showed that HAT-7, a rat dental epithelial cell line, expressed Mel1aR and its expression levels increased after the cells reached confluence. These results strongly suggest that melatonin may play a physiological role in tooth development/growth by regulating the cellular function of odontogenic cells in tooth germs.

Keywords

Melatonin Melatonin 1a receptor Tooth development Immunohistochemistry Gene expression 

Notes

Acknowledgments

This work was supported by a Grant-in-Aid for Scientific Research (16390591, 17791467 and 21592575) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

References

  1. Al-Ghoul WM, Herman MD, Dubocovich ML (1998) Melatonin receptor subtype expression in human cerebellum. Neuroreport 9:4063–4068CrossRefPubMedGoogle Scholar
  2. Batmanabane M, Ramesh KG (1996) Effect of exogenous melatonin on the onset of puberty in female albino rats. Anat Rec 245:519–524CrossRefPubMedGoogle Scholar
  3. Cagnacci A, Soldani R, Yen SS (1995) Melatonin enhances cortisol levels in aged but not young women. Eur J Endocrinol 133:691–695CrossRefPubMedGoogle Scholar
  4. Dollins AB, Zhdanova IV, Wurtman RJ, Lynch HJ, Deng MH (1994) Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance. Proc Natl Acad Sci USA 91:1824–1828CrossRefPubMedGoogle Scholar
  5. Drew JE, Williams LM, Hannah LT, Barrett P, Abramovich DR, Morgan PJ (1997) Identification and characterisation of 2-[125I]iodomelatonin binding and Mel1a melatonin receptor expression in the human fetal leptomeninges. Brain Res 761:87–92CrossRefPubMedGoogle Scholar
  6. Drew JE, Williams LM, Hannah LT, Barrett P, Abramovich DR (1998) Melatonin receptors in the human fetal kidney: 2-[125I]iodomelatonin binding sites correlated with expression of Mel1a and Mel1b receptor genes. J Endocrinol 156:261–267CrossRefPubMedGoogle Scholar
  7. Esquifino AI, Villanua MA, Agrasal C (1987) Effect of neonatal melatonin administration on sexual development in the rat. J Steroid Biochem 27:1089–1093CrossRefPubMedGoogle Scholar
  8. Forsling ML, Wheeler MJ, Williams AJ (1999) The effect of melatonin administration on pituitary hormone secretion in man. Clin Endocrinol 51:637–642CrossRefGoogle Scholar
  9. Garcia-Maurino S, Pozo D, Calvo JR, Guerrero JM (2000) Correlation between nuclear melatonin receptor expression and enhanced cytokine production in human lymphocytic and monocytic cell lines. J Pineal Res 29:129–137CrossRefPubMedGoogle Scholar
  10. Gilbert SF (2000) Developmental biology, 6th edn. Sinauer Associates, Sunderland, pp 420–422Google Scholar
  11. Guerrero JM, Reiter RJ (2002) Melatonin–immune system relationships. Curr Top Med Chem 2:167–179CrossRefPubMedGoogle Scholar
  12. Hill SM, Blask DE (1988) Effects of the pineal hormone melatonin on the proliferation and morphological characteristics of human breast cancer cells (MCF-7) in culture. Cancer Res 48:6121–6126PubMedGoogle Scholar
  13. Isogai Y, Akatsu T, Ishizuya T, Yamaguchi A, Hori M, Takahashi N, Suda T (1996) Parathyroid hormone regulates osteoblast differentiation positively or negatively depending on the differentiation stages. J Bone Miner Res 11:1384–1393CrossRefPubMedGoogle Scholar
  14. Jernvall J, Thesleff I (2000) Reiterative signaling and patterning in mammalian tooth morphogenesis. Mech Dev 92:19–29CrossRefPubMedGoogle Scholar
  15. Jilka RL, Takahashi K, Munshi M, William DC, Roberson PK, Manolagas SC (1998) Loss of estrogen upregulates osteoblastogenesis in the murine bone marrow: evidence for autonomy from factors released during bone resorption. J Clin Invest 101:1942–1950CrossRefPubMedGoogle Scholar
  16. Kassem M, Mosekilde L, Eriksen EF (1994) Growth hormone stimulates proliferation of normal human bone marrow stromal osteoblast precursor cells in vitro. Growth Regul 4:131–135PubMedGoogle Scholar
  17. Kawano S, Morotomi T, Toyono T, Nakamura N, Uchida T, Ohishi M, Toyoshima K, Harada H (2002) Establishment of dental epithelial cell line (HAT-7) and the cell differentiation dependent on notch signaling pathway. Connect Tissue Res 43:409–412PubMedGoogle Scholar
  18. Kennaway DJ, Rowe SA (1995) Melatonin binding sites and their role in seasonal reproduction. J Reprod Fertil Suppl 49:423–435PubMedGoogle Scholar
  19. Kostoglou-Athanassiou I, Treacher DF, Wheeler MJ, Forsling ML (1998) Melatonin administration and pituitary hormone secretion. Clin Endocrinol 48:31–37CrossRefGoogle Scholar
  20. Koyama H, Nakade O, Takeda Y, Kaku T, William Lau KH (2002) Melatonin at pharmacological doses increases bone mass by suppressing resorption through down-regulation of the RANKL-mediated osteoclast formation and activation. J Bone Miner Res 17:1219–1229CrossRefPubMedGoogle Scholar
  21. León J, Acuña-Castroviejo D, Escames D, Tan DX, Reiter RJ (2005) Melatonin mitigates mitochondrial malfunction. J Pineal Res 38:1–9CrossRefPubMedGoogle Scholar
  22. Lerner AB, Case JD, Takahashi Y, Lee T, Mori W (1958) Isolation of melatonin, the pineal gland factor that lightens melanocytes. J Am Chem Soc 80:2587CrossRefGoogle Scholar
  23. Lynch HJ, Brzezinski A, Deng MH, Lieberman HR, Wurtman RJ (1987) Effect of behavioural and physiological variables on melatonin secretion in humans. In: Reiter RJ, Fraschini F (eds) Advances in pineal research, vol 2. Libbey, London, pp 181–190Google Scholar
  24. Machida M, Dubousset J, Yamada T, Kimura J, Saito M, Shiraishi T, Yamagishi M (2006) Experimental scoliosis in melatonin-deficient C57BL/6J mice without pinealectomy. J Pineal Res 41:1–7CrossRefPubMedGoogle Scholar
  25. Martínez-Campa C, Alonso-González C, Mediavilla MD, Cos S, González A, Ramos S, Sánchez-Barceló EJ (2006) Melatonin inhibits both ERa activation and breast cancer cell proliferation induced by a metalloestrogen, cadmium. J Pineal Res 40:291–294CrossRefPubMedGoogle Scholar
  26. McArthur AJ, Hunt AE, Gillette MU (1997) Melatonin action and signal transduction in the rat suprachiasmatic circadian clock: activation of protein kinase C at dusk and dawn. Endocrinology 138:627–634CrossRefPubMedGoogle Scholar
  27. Nakade O, Koyama H, Ariji H, Yajima A, Kaku T (1999) Melatonin stimulates proliferation and type I collagen synthesis in human bone cells in vitro. J Pineal Res 27:106–110CrossRefPubMedGoogle Scholar
  28. Nakamura T, Hanada K, Tamura M, Shibanushi T, Nigi H, Tagawa M, Fukumoto S, Matsumoto T (1995) Stimulation of endosteal bone formation by systemic injections of recombinant basic fibroblast growth factor in rats. Endocrinology 136:1276–1284CrossRefPubMedGoogle Scholar
  29. Pozo D, Delgado M, Fernandez-Santos JM, Calvo JR, Gomariz BP, Martin-Lacave I, Ortiz GG, Guerrero JM (1997) Expression of the Mel1a-melatonin receptor mRNA in T and B subsets of lymphocytes from rat thymus and spleen. FASEB J 11:466–473PubMedGoogle Scholar
  30. Raghavendra V, Singh V, Kulkarni SK, Agrewala JN (2001) Melatonin enhances Th2 cell mediated immune responses: lack of sensitivity to reversal by naltrexone or benzodiazepine receptor antagonists. Mol Cell Biochem 221:57–62CrossRefPubMedGoogle Scholar
  31. Redman J, Armstrong S, Ng KT (1983) Free-running activity rhythms in the rat: entrainment by melatonin. Science 219:1089–1091CrossRefPubMedGoogle Scholar
  32. Reiter RJ (1991) Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocr Rev 12:151–180CrossRefPubMedGoogle Scholar
  33. Reiter RJ, Oh CS, Fujimori O (1996) Melatonin its intracellular and genomic actions. Trends Endcrinol Metab 7:22–27CrossRefGoogle Scholar
  34. Reppert SM, Weaver DR, Ebisawa T (1994) Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. Neuron 13:1177–1185CrossRefPubMedGoogle Scholar
  35. Reppert SM, Godson C, Mahle CD, Weaver DR, Slaugenhaupt SA, Gusella JF (1995) Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. Proc Natl Acad Sci USA 92:8734–8738CrossRefPubMedGoogle Scholar
  36. Roth JA, Kim BG, Lin WL, Cho MI (1999) Melatonin promotes osteoblast differentiation and bone formation. J Biol Chem 274:22041–22047CrossRefPubMedGoogle Scholar
  37. Sánchez-Barceló EJ, Cos S, Mediavilla MD, Martínez-Campa C, González A, Alonso-González C (2005) Melatonin-estrogen interaction in breast cancer. J Pieal Res 38:217–222Google Scholar
  38. Satomura K, Tobiume S, Tokuyama R, Yamasaki Y, Kudoh K, Maeda E, Nagayama M (2007) Melatonin at pharmacological doses enhances human osteoblastic differentiation in vitro and promotes mouse cortical bone formation in vivo. J Pineal Res 42:231–239CrossRefPubMedGoogle Scholar
  39. Shinar DM, Endo N, Halperin D, Rodan GA, Weunreb M (1993) Differential expression of insulin-like growth factor-I (IGF-I) and IGF-II messenger ribonucleic acid in growing rat bone. Endocrinology 132:1158–1167CrossRefPubMedGoogle Scholar
  40. Smith TM (2006) Experimental determination of the periodicity of incremental features in enamel. J Anat 208:99–113CrossRefPubMedGoogle Scholar
  41. Tan DX, Manchester LC, Terron MP, Flores LJ, Reiter RJ (2007) One molecule, many derivatives: a never-ending interaction of melatonin with reactive oxygen and nitrogen species? J Pineal Res 42:28–42CrossRefPubMedGoogle Scholar
  42. Ten Cate AR (1994) Oral histology, 4th edn. Mosby, St. Louis, pp 58–80Google Scholar
  43. Thesleff I, Mikkola M (2002) The role of growth factors in tooth development. Int Rev Cytol 217:93–135CrossRefPubMedGoogle Scholar
  44. Thesleff I, Partanen AM, Vainio S (1991) Epithelial–mesenchymal interactions in tooth morphogenesis: the roles of extracellular matrix, growth factors, and cell surface receptors. J Craniofac Genet Dev Biol 11:229–237PubMedGoogle Scholar
  45. Turgut M, Kaplan S, Turgut AT, Hüseyin A, Güvenç T, Emre C, Serpil E (2005) Morphological, stereological and radiological changes in pinealectomized chicken cervical vertebrae. J Pineal Res 39:392–399CrossRefPubMedGoogle Scholar
  46. Yamaguchi A, Katagiri T, Ikeda T, Wozney JM, Rosen V, Wang EA, Kahn AJ, Suda T, Yoshiki S (1991) Recombinant human bone morphogenetic protein-2 stimulates osteoblastic maturation and inhibits myogenic differentiation in vitro. J Cell Biol 113:681–687CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Shuku Kumasaka
    • 1
  • Masashi Shimozuma
    • 1
  • Tadafumi Kawamoto
    • 2
  • Kenji Mishima
    • 3
  • Reiko Tokuyama
    • 1
  • Yoko Kamiya
    • 1
  • Purevsuren Davaadorj
    • 4
  • Ichiro Saito
    • 3
  • Kazuhito Satomura
    • 1
  1. 1.Second Department of Oral and Maxillofacial Surgery, Department of Oral Medicine, School of Dental MedicineTsurumi UniversityYokohamaJapan
  2. 2.RI Research Center, School of Dental MedicineTsurumi UniversityYokohamaJapan
  3. 3.Department of Pathology, School of Dental MedicineTsurumi UniversityYokohamaJapan
  4. 4.Department of Oral and Maxillofacial Surgery, Institute of Health BiosciencesThe University of Tokushima Graduate SchoolTokushimaJapan

Personalised recommendations