Morphology of Tooth and Smad4 Expression in NFI-C Deficient Mouse

Nuclear Factor I-C 결손생쥐에서 치아의 형태학적 변화와 Smad4의 발현

  • Bae, Hyun-Sook (Dept. of Dental Hygiene, Namseoul University) ;
  • Kim, Hye-Mi (Dept. of Dental Hygiene, Namseoul University) ;
  • Cho, Young-Sik (Dept. of Dental Hygiene, Namseoul University) ;
  • Park, Su-Jin (Dept. of Oral Histology-Developmental Biology & Dental Research Institute, School of Dentistry, Seoul National University) ;
  • Choi, Moon-Sil (Dept. of Dental Hygiene, Song Won University College)
  • 배현숙 (남서울대학교 치위생학과) ;
  • 김혜미 (남서울대학교 치위생학과) ;
  • 조영식 (남서울대학교 치위생학과) ;
  • 박수진 (서울대학교 치과대학 구강조직 발생생물학교실) ;
  • 최문실 (송원대학교 치위생과)
  • Received : 2010.08.12
  • Accepted : 2010.10.22
  • Published : 2010.10.30

Abstract

Over expression of TGF-${\beta}1$ revealed the same phenotype as NFI-C deficient mouse. It has been reported that NFI-C deficient mice demonstrated abnormal odontoblast differentiation and aberrant dentin formation during root development. In the present study, in order to investigate the histological differences between wild type (WT) mouse and NFI-C deficient mouse, we compared morphological characteristics and smad4 expression between those mice. Hematoxyline-eosin (H-E) staining was used to investigate morphological changes and immunohistochemistry was also performed to observe the Smad4 expression pattern. In H-E staining, incisor of NFI-C deficient mouse showed an open area in the lingual root, irregular odontoblasts and osteodentin. Also, NFI-C deficient mouse showed short root and osteodentin in molar. In addition, Smad4 protein was strongly expressed in NFI-C deficient mouse compared with wild type. These findings suggest that NFI-C deficiency affects odontoblast differentiation and result in the formation of abnormal roots. Therefore, balancing between NFI-C and TGF-${\beta}$ signaling including Smad4 is important for the regulation of normal odontoblast differentiation and dentin formation.

본 연구는 상아모세포의 분화, 상아질의 형성, 치근 형성에 중요한 역할을 하는 NFI-C가 치아에 미치는 영향과 NFI-C 결손 생쥐에서 NFI-C와 TGF-${\beta}$의 신호전달물질인 Smad4의 발현양상을 알아보았다. 이를 위해 NFI-C 결손 생쥐치아를 광학 현미경과 면역조직적 화학방법을 사용하여 다음과 같은 결과를 얻었다. 1. NFI-C 결손생쥐는 전치부의 경우 법랑질이 있는 치관 부위는 상아질이 정상적으로 형성되었지만 법랑질이 없는 설면 부위는 개방되어 있었고 뼈모양 상아질이 관찰되었다. 2. NFI-C 결손생쥐는 구치부의 경우 법랑질이 있는 치관 부위는 상아질이 정상적으로 형성되었지만 법랑질이 없는 치근부위의 치근은 짧아졌고 상아모세포의 수가 줄었으며 약간의 뼈모양 상아질이 관찰되었다. 이는 NFI-C결손이 상아모세포 분화에 영향을 끼쳐 비정상적인 치근을 만드는 것을 보여준다. 3. NFI-C 결손생쥐의 Smad4 발현은 정상 생쥐에 비해서 핵에 더 많은 발현을 보였다. 이는 Smad4가 NFI-C와 TGF-${\beta}$의 신호전달물질로서 그 사이에서 균형을 맞추면서 상아모세포 분화에 영향을 미친다는 것을 보여준다.

Keywords

References

  1. Mina M, Kollar EJ: The induction of odontogenesis in nondental mesenchyme combined with early murine mandibular arch epithelium. Arch Oral Biol 32: 123-127, 1987. https://doi.org/10.1016/0003-9969(87)90055-0
  2. Maas R, Bei M: The genetic control of early tooth development. Crit Rev Oral Biol Med 8(1): 4-39, 1997. https://doi.org/10.1177/10454411970080010101
  3. Ruch JV, Lesot H, Begue-Kirn C: Odontoblast differenciation. Int J Dev Biol 39(1): 51-68, 1995.
  4. Antonio Nanci: Ten cate's oral histology: Development, structure, and function. 7th ed. MOSBY. St. Louis, pp. 89-103, 156-166, 2007.
  5. Garant PR: The organization of microtubules within rat odontoblast processes revealed by perfusion fixation with glutaraldehyde. Arch Oral Biol 17(7): 1047-1058, 1972. https://doi.org/10.1016/0003-9969(72)90179-3
  6. Bosshardt DD, Nanci A: Hertwig's epithelial root sheath matrix proteins and initiation of cemetogenesis in porcine teeth. J Periodontal 31(3): 184-192, 2004. https://doi.org/10.1111/j.0303-6979.2004.00473.x
  7. Steele-parkins G et al.: Essental role NFI-C/CTF transcription _ replication factor in tooth root development. Mol Cell Biol 23(3): 1075-1084, 2003. https://doi.org/10.1128/MCB.23.3.1075-1084.2003
  8. Chaudhry AZ, Lyons GE, Gronostajski RM: Expression patterns of the four nuclear factor I genes during mouse embryogenesis indicate a potential role in development. Dev Dye 208(3): 313-25, 1997. https://doi.org/10.1002/(SICI)1097-0177(199703)208:3<313::AID-AJA3>3.0.CO;2-L
  9. Chaudhry AZ, Vitullo AD, Gronostajski RM: Nuclear factor I (NFI) isoforms differentially activate simple versus complex NFI-responsive promoters. J Biol Chem 273(29): 18538-18546, 1998. https://doi.org/10.1074/jbc.273.29.18538
  10. Mukhopadhyay SS et al.: Differential interactions of specific nuclear factor I isoforms with the glucocorticoid receptor and STAT5 in the cooperative regulation of WAP gene transcription. Mol Cell Biol 21(20): 5859-6869, 2001.
  11. Ling G et al.: Transcriptional regulation of rat CYP2A3 by nuclear factor 1: Identification of a novel NFI-A isoform, and evidence for tissue-selective interaction of NFI with the CYP2A3 promoter in vivo. J Biol Chem 279(27): 27888-95, 2004. https://doi.org/10.1074/jbc.M403705200
  12. Shu T et al.: Abnormal development of forebrain midline glia and commissural projections in Nfia knock-out mice. J Neurosci Jan 23(1): 203-12, 2003.
  13. Park JC et al.: Nfic gene disruption inhibits differentiation of odontoblasts responsible for root formation and results in formation of short and abnormal roots in mice. J Periodontol 78(9): 1795-802, 2007. https://doi.org/10.1902/jop.2007.060363
  14. 배현숙 등: 상아모세포 분화과정에서 nuclear factorI-C의 역할. 대한구강병리학회지 29(2): 83-82, 2005.
  15. 윤성호 등: Nuclear Factor I-C 과발현과 발현억제가 mdpc-23 상아모세포주의 상아질 기질유전자 발현에 미치는 영향. 대한해부학회지 40(2): 127-135, 2007.
  16. Thyagarajan T et al.: Reduced expression of dentin sialophosphoprotein is associated with dysplastic dentin in mice over expressing transforming growth factor-beta 1 in teeth. J Biol Chem 276(14): 11016-20, 2001. https://doi.org/10.1074/jbc.M010502200
  17. 배현숙, 조영식: NFI-C가 Smad와 TGF-${\beta}$R1이 발현에 미치는 영향. 한국치위생과학회지 9(4) 427-433, 2009.
  18. Lee KY, Bae SC: TGF-beta-dependent cell growth arrest and apoptosis. J Biochem Mol Biol 35(1): 47-53, 2002. https://doi.org/10.5483/BMBRep.2002.35.1.047
  19. Bruce Alberts et al.: Molecular biology of the cell. 5th ed. Garland Science, New York, pp. 393-940, 2008.
  20. Yuanrong Gao et al.: Disruption of Smad4 in odontoblast causes multiple keratocystic odontogenic tumors and tooth malformation in mice. Mol Cell Biol 29(21): 1942-1944, 2009.
  21. Aristidis M, Serhiy S, Carl-Henrik H: Smad regulation in TGF-${\beta}$ signal transduction. J Cell Sci 114(24): 4363-4366, 2001.