DOI QR코드

DOI QR Code

Roles of Sonic Hedgehog Signaling During Tooth Root and Periodontium Formation

치근 및 치주조직 형성과정 동안 Sonic Hedgehog signaling의 역할

  • Hwang, Jaewon (Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University) ;
  • Cho, Eui-sic (Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University) ;
  • Yang, Yeonmi (Department of Pediatric Dentistry and Institute of Oral Bioscience, School of Dentistry, Chonbuk National University)
  • 황재원 (전북대학교 치과대학 구강해부조직학교실 및 구강생체과학연구소) ;
  • 조의식 (전북대학교 치과대학 구강해부조직학교실 및 구강생체과학연구소) ;
  • 양연미 (전북대학교 치과대학 소아치과학교실 및 구강생체과학연구소)
  • Received : 2017.08.04
  • Accepted : 2017.09.22
  • Published : 2018.05.31

Abstract

The aim of this study was to understand the roles of Sonic Hedgehog (SHH) signaling during tooth root and periodontium formation. In this study, we generated the dental mesenchyme-specific Smoothened (Smo) activated/inactivated mice with the activity of Cre recombinase under the control of osteocalcin promoter. In the Smo activated mutant molar sections at the postnatal 28 days, we found extremely thin root dentin and widened pulp chamber. Picrosirius red staining showed loosely arranged fibers in the periodontal space and decreased cellular cementum with some root resorption. Immunohistochemical staining showed less localization of matrix proteins such as Bsp, Dmp1, Pstn, and Ank in the cementum, periodontal ligament, and/or cementoblast. In the Smo inactivated mutant mouse, there was not any remarkable differences in the localization of these matrix proteins compared with the wild type. These findings suggest that adequate suppressing regulation of SHH signaling is required in the development of tooth root and periodontium.

본 연구는 치근 및 치주조직의 형성과정동안 Sonic Hedgehog (SHH) signaling의 역할에 대해 알아보고자 치성간엽에서 조직특이적으로 Smoothened (Smo)가 활성화 또는 차단되는 mouse를 제작하여 분석하였다. 생후 28일경 Smo 활성화모델에서는 H-E 염색 시 얇은 두께의 치근상아질, 넓어진 치수강, 치주인대공간에 느슨하게 배열되어있는 섬유들이 관찰되었다. 면역조직화학염색 시 Smo 활성화모델은 wild type mouse와 비교하여 백악질, 치주인대 그리고/또는 백악모세포의 표식자인 Bsp, Dmp1, Periostin, Ank 같은 기질 단백질들의 발현이 현저히 감소하였다. 그러나 Smo 차단모델은 wild type mouse와 비교하여 이러한 기질 단백질들의 발현에 차이가 보이지 않았다. 본 연구를 통하여 치근 및 치주조직의 정상적인 형성과정에 낮은 수준으로 조절되는 SHH signaling이 필요하다는 것을 확인할 수 있었다.

Keywords

References

  1. Cohen MM Jr : The hedgehog signaling network. Am J Med Genet, 123:5-28, 2003.
  2. Ingham PW, McMahon AP : Hedgehog signaling in animal development: paradigms and principles. Gene Dev, 15:3059-3087, 2001. https://doi.org/10.1101/gad.938601
  3. Khan M, Seppala M, Cobourne MT, et al. : Hedgehog pathway gene expression during early development of the molar tooth root in the mouse. Gene Expr Patterns, 7:239-243, 2007. https://doi.org/10.1016/j.modgep.2006.10.001
  4. Huang XF, Xu X, Chai Y, et al. : Smad4-Shh-Nfic signaling cascade-mediated epithelial- mesenchymal interaction is crucial in regulationg tooth root development. J Bone Miner Res, 25:1167-1178, 2010.
  5. Nakatomi M, Morita I, Ota MS, et al. : Sonic Hedgehog signaling is important in tooth root development. J Dent Res, 85:427-431, 2006. https://doi.org/10.1177/154405910608500506
  6. Kim TH, Bae CH, Cho ES, et al. : Nfic regulates tooth root patterning and growth. Anat Cell Biol, 48:188-194, 2015. https://doi.org/10.5115/acb.2015.48.3.188
  7. Zhang XM, Ramalho-Santos M, McMahon AP : Smoothened mutants reveal redundant roles for Shh and Ihh signaling including regulation of L/R asymmetry by the mouse node. Cell, 105:781-792, 2001. https://doi.org/10.1016/S0092-8674(01)00385-3
  8. Jeong J, Mao J, McMahon AP, et al. : Hedgehog signaling in the neural crest cells regulates the patterning and growth of facial primordia. Genes Dev, 18:937-951, 2004. https://doi.org/10.1101/gad.1190304
  9. Long F, Zhang XM, McMahon AP, et al. : Genetic maniulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation. Development, 128:5099-5108, 2001.
  10. Tan X, Weng T, Yang X, et al. : Smad4 is required for maintaining normal murine postnatal bone homeostasis. J Cell Sci, 120:2162-2170, 2007. https://doi.org/10.1242/jcs.03466
  11. Hardcastle Z, Mo R, Sharpe PT, et al. : The SHH signalling pathway in tooth development: defects in Gli2 and Gli3 mutants. Development, 125:2803-2811, 1998.
  12. Thesleff I : The genetic basis of tooth development and dental defects. Am J Med Genet, 140:2530-2535, 2006.
  13. Slavkin HC, Boyde A : Cementum: an epithelial secretory product? (abstract). J Dent Res, 53:157, 1975.
  14. Hammarstrom L : Enamel matrix, cementum development and regeneration. J Clin Periodontol, 24:658-668, 1997. https://doi.org/10.1111/j.1600-051X.1997.tb00247.x
  15. Aukhil I, Nishimura K, Fernyhough W : Experimental regeneration of the periodontium. Crit Rev Oral Biol Med, 1:101-115, 1990. https://doi.org/10.1177/10454411900010020101
  16. Huang X, Bringas P Jr, Chai Y, et al. : Fate of HERS during tooth root development. Dev Biol, 334:22-30, 2009. https://doi.org/10.1016/j.ydbio.2009.06.034
  17. Gritli-Linde A, Bei M, McMahon AP, et al. : Shh signaling within the dental epithelium is necessary for cell proliferation, growth and polarization. Development, 129:5323-5337, 2002. https://doi.org/10.1242/dev.00100
  18. Bae WJ, Auh QS, Lim HC, et al. : Sonic Hedgehog Promotes Cementoblastic Differentiation via Activating the BMP Pathways. Calcif Tissue Int, 99:396-407, 2016. https://doi.org/10.1007/s00223-016-0155-1
  19. Lim WH, Liu B, Cheng D, et al. : Down regulation of Wnt causes root resorption. Am J Orthod Dentofacial Orthop, 146:337-45, 2014. https://doi.org/10.1016/j.ajodo.2014.05.027
  20. Kim TH, Lee JY, Cho ES, et al. : Constitutive stabilization of ${\beta}$-catenin in the dental mesenchyme leads to excessive dentin and cementum formation. Biochem Biophys Res Commun, 412:549-555, 2011. https://doi.org/10.1016/j.bbrc.2011.07.116
  21. Kim TH, Bae CH, Cho ES, et al. : ${\beta}$-catenin is required in odontoblasts for tooth root formation. J Dent Res, 92:215-221, 2013. https://doi.org/10.1177/0022034512470137
  22. Martinez C, Smith PC, Palma V, et al. : Sonic Hedgehog stimulates proliferation of human periodontal ligament stem cells. J Dent Res, 90:483-488, 2011. https://doi.org/10.1177/0022034510391797