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Comparative Gene-Expression Analysis of Periodontal Ligament and Dental Pulp in the Human Permanent Teeth

사람 영구치에서 치주인대 및 치수 조직의 유전자 발현에 대한 비교 연구

  • Lee, Suk Woo (Department of Pediatric Dentistry, College of Dentistry, Yonsei University) ;
  • Jeon, Mijeong (Department of Pediatric Dentistry, College of Dentistry, Yonsei University) ;
  • Lee, Hyo-Seol (Department of Pediatric Dentistry, College of Dentistry, Kyunghee University) ;
  • Song, Je Seon (Department of Pediatric Dentistry, College of Dentistry, Yonsei University) ;
  • Son, Heung-Kyu (Department of Pediatric Dentistry, College of Dentistry, Yonsei University) ;
  • Choi, Hyung-Jun (Department of Pediatric Dentistry, College of Dentistry, Yonsei University) ;
  • Jung, Han-Sung (Department of Oral Biology, College of Dentistry, Yonsei University) ;
  • Moon, Seok-Jun (Department of Oral Biology, College of Dentistry, Yonsei University) ;
  • Park, Wonse (Department of General Dentistry, College of Dentistry, Yonsei University) ;
  • Kim, Seong-Oh (Department of Pediatric Dentistry, College of Dentistry, Yonsei University)
  • 이석우 (연세대학교 치과대학 소아치과학교실) ;
  • 전미정 (연세대학교 치과대학 소아치과학교실) ;
  • 이효설 (경희대학교 치과대학 소아치과학교실) ;
  • 송제선 (연세대학교 치과대학 소아치과학교실) ;
  • 손흥규 (연세대학교 치과대학 소아치과학교실) ;
  • 최형준 (연세대학교 치과대학 소아치과학교실) ;
  • 정한성 (연세대학교 치과대학 구강생물학교실) ;
  • 문석준 (연세대학교 치과대학 구강생물학교실) ;
  • 박원서 (연세대학교 치과대학 통합진료학교실) ;
  • 김성오 (연세대학교 치과대학 소아치과학교실)
  • Received : 2015.05.21
  • Accepted : 2015.10.27
  • Published : 2016.05.31

Abstract

There is no genetic activity information with the functions of dental pulp and periodontal ligament in human. The purpose of this study was to identify the gene-expression profiles of, and the molecular biological differences between periodontal ligament and dental pulp obtained from human permanent teeth. cDNA microarray analysis identified 347 genes with a fourfold or greater difference in expression level between the two tissue types 83 and 264, of which were more plentiful in periodontal ligament and dental pulp, respectively. Periodontal ligament exhibited strong expression of genes related to collagen synthesis (FAP), collagen degradation (MMP3, MMP9, and MMP13), and bone development and remodeling (SSP1, BMP3, ACP5, CTSK, and PTHLH). Pulp exhibited strong expression of genes associated with calcium ions (CALB1, SCIN, and CDH12) and the mineralization and formation of enamel and dentin (SPARC/SPOCK3, PHEX, AMBN, and DSPP). Among these genes, SPP1, SPARC/SPOCK3, AMBN, and DSPP were well known in dental research. However, the other genes are the newly found and it may help to find a good source of regenerative therapy if further study is performed.

이전 연구에서 사람의 치수와 치주인대의 기능에 대한 구체적인 3만 2천여개의 인체 유전자의 RNA 활성 정보는 없었다. 본 연구의 목적은 사람 영구치에서 얻은 치주인대와 치수 조직 내의 RNA 유전자 발현을 보고하고 각각의 분자생물학적인 차이를 알아보는 것이다. cDNA 미세배열분석에서 두 조직 사이의 유전자 발현 수준에서 4배 이상 차이나는 유전자는 347개로 밝혀졌으며, 치주인대와 치수에서 각각 83개, 264개의 유전자 발현이 4배 이상 차이난다는 것을 보여주었다. 치주인대는 교원질 합성 (FAP), 교원질 분해 (MMP3, MMP9와 MMP13), 골 형성 및 개조 (SPP1, BMP3, ACP5, CTSK와 PTHLH)와 관련된 유전자가 강하게 발현되었다. 반면 치수조직은 칼슘 이온 (CALB1, SCIN와 CDH12)과 법랑질 또는 상아질의 광화 및 형성 (SPARC/SPOCK3, PHEX, AMBN과 DSPP)와 관련한 유전자의 발현이 높게 나타났다. 이들 유전자 중 SPP1, SPARC/SPOCK3, AMBN, DSPP 등의 유전자는 치아의 기능과 관련해서 잘 알려져 있지만, 다른 유전자들은 microarray 분석을 통해서 새롭게 발견된 유전자이다. 이 유전자들은 추가적인 연구가 수행된다면 재생 치료의 좋은 요인을 찾는데 도움이 될 것으로 생각된다.

Keywords

References

  1. Demarco FF, Conde MC, Cavalcanti BN, et al. : Dental pulp tissue engineering. Braz Dent J, 22:3-13, 2011. https://doi.org/10.1590/S0103-64402011000100001
  2. Caton J, Bostanci N, Remboutsika E, et al. : Future dentistry: cell therapy meets tooth and periodontal repair and regeneration. J Cell Mol Med, 15:1054-1065, 2011. https://doi.org/10.1111/j.1582-4934.2010.01251.x
  3. Danesh-Meyer MJ : Tissue engineering in periodontics and implantology using rhBMP-2. Ann R Australas Coll Dent Surg, 15:144-149, 2000.
  4. Song JS, Hwang DH, Kim SO, et al. : Comparative gene expression analysis of the human periodontal ligament in deciduous and permanent teeth. PLoS One, 8:e61231, 2013. https://doi.org/10.1371/journal.pone.0061231
  5. Xie YF, Shu R, Jiang SY, et al. : Comparison of microRNA profiles of human periodontal diseased and healthy gingival tissues. Int J Oral Sci, 3:125-134, 2011. https://doi.org/10.4248/IJOS11046
  6. Lee YH, Na HS, Jeong SY, et al. : Comparison of inflammatory microRNA expression in healthy and periodontitis tissues. Biocell, 35:43-49, 2011.
  7. Han X, Amar S : Identification of genes differentially expressed in cultured human periodontal ligament fibroblasts vs. human gingival fibroblasts by DNA microarray analysis. J Dent Res, 81:399-405, 2002. https://doi.org/10.1177/154405910208100609
  8. de Araujo RM, Oba Y, Moriyama K : Identification of genes related to mechanical stress in human periodontal ligament cells using microarray analysis. J Periodontal Res, 42:15-22, 2007. https://doi.org/10.1111/j.1600-0765.2006.00906.x
  9. Paakkonen V, Ohlmeier S, Bergmann U, et al. : Analysis of gene and protein expression in healthy and carious tooth pulp with cDNA microarray and two-dimensional gel electrophoresis. Eur J Oral Sci, 113:369-379, 2005. https://doi.org/10.1111/j.1600-0722.2005.00237.x
  10. McLachlan JL, Smith AJ, Bujalska IJ, Cooper PR : Gene expression profiling of pulpal tissue reveals the molecular complexity of dental caries. Biochim Biophys Acta, 1741:271-281, 2005. https://doi.org/10.1016/j.bbadis.2005.03.007
  11. Paakkonen V, Vuoristo JT, Salo T, Tjaderhane L : Comparative gene expression profile analysis between native human odontoblasts and pulp tissue. Int Endod J, 41:117-127, 2008.
  12. Heikinheimo K, Jee KJ, Niini T, et al. : Gene expression profiling of ameloblastoma and human tooth germ by means of a cDNA microarray. J Dent Res, 81:525-530, 2002. https://doi.org/10.1177/154405910208100805
  13. Lee HS, Lee J, Kim SO, et al. : Comparative geneexpression analysis of the dental follicle and periodontal ligament in humans. PLoS One, 8:e84201, 2013. https://doi.org/10.1371/journal.pone.0084201
  14. Gottlow J, Nyman S, Karring T, Lindhe J : New attachment formation as the result of controlled tissue regeneration. J Clin Periodontol, 11:494-503, 1984. https://doi.org/10.1111/j.1600-051X.1984.tb00901.x
  15. Mitchell DL, West JD : Attempted orthodontic movement in the presence of suspected ankylosis. Am J Orthod, 68:404-411, 1975. https://doi.org/10.1016/0002-9416(75)90181-5
  16. Lekic P, McCulloch CA: Periodontal ligament cell population: the central role of fibroblasts in creating a unique tissue. Anat Rec, 245:327-341, 1996. https://doi.org/10.1002/(SICI)1097-0185(199606)245:2<327::AID-AR15>3.0.CO;2-R
  17. Abrahao IJ, Martins MD, Katayama E, et al. : Collagen analysis in human tooth germ papillae. Braz Dent J, 17:208-212, 2006. https://doi.org/10.1590/S0103-64402006000300006
  18. Gronthos S, Mankani M, Brahim J, et al. : Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A, 97:13625-13630, 2000. https://doi.org/10.1073/pnas.240309797
  19. Shi M, Yu DH, Chen Y, et al. : Expression of fibroblast activation protein in human pancreatic adenocarcinoma and its clinicopathological significance. World J Gastroenterol, 18:840-846, 2012. https://doi.org/10.3748/wjg.v18.i8.840
  20. Boushell LW, Kaku M, Mochida Y, Yamauchi M : Distribution and relative activity of matrix metalloproteinase-2 in human coronal dentin. Int J Oral Sci, 3:192-199, 2011. https://doi.org/10.4248/IJOS11070
  21. Hakki SS, Hakki EE, Nohutcu RM : Regulation of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases by basic fibroblast growth factor and dexamethasone in periodontal ligament cells. J Periodontal Res, 44:794-802, 2009. https://doi.org/10.1111/j.1600-0765.2008.01192.x
  22. Choi ST, Kim JH, Kang EJ, et al. : Osteopontin might be involved in bone remodelling rather than in inflammation in ankylosing spondylitis. Rheumatology (Oxford), 47:1775-1779, 2008. https://doi.org/10.1093/rheumatology/ken385
  23. Daluiski A, Engstrand T, Bahamonde ME, et al. : Bone morphogenetic protein-3 is a negative regulator of bone density. Nat Genet, 27:84-88, 2001.
  24. Choi S, Cho TJ, Kwon SK, et al. : Chondrogenesis of periodontal ligament stem cells by transforming growth factor-beta3 and bone morphogenetic protein-6 in a normal healthy impacted third molar. Int J Oral Sci, 5:7-13, 2013. https://doi.org/10.1038/ijos.2013.19
  25. Baumbach GA, Saunders PT, Ketcham CM, et al. : Uteroferrin contains complex and high mannose-type oligosaccharides when synthesized in vitro. Mol Cell Biochem, 105:107-117, 1991.
  26. Ouyang H, McCauley LK, Berry JE, et al. : Parathyroid hormone-related protein regulates extracellular matrix gene expression in cementoblasts and inhibits cementoblast-mediated mineralization in vitro. J Bone Miner Res, 15:2140-2153, 2000. https://doi.org/10.1359/jbmr.2000.15.11.2140
  27. Wasserman RH, Taylor AN : Vitamin d3-induced calcium-binding protein in chick intestinal mucosa. Science, 152:791-793, 1966. https://doi.org/10.1126/science.152.3723.791
  28. Selig S, Bruno S, Scharf JM, et al. : Expressed cadherin pseudogenes are localized to the critical region of the spinal muscular atrophy gene. Proc Natl Acad Sci U S A, 92:3702-3706, 1995. https://doi.org/10.1073/pnas.92.9.3702
  29. Yan Q, Sage EH : SPARC, a matricellular glycoprotein with important biological functions. J Histochem Cytochem, 47:1495-1506, 1999. https://doi.org/10.1177/002215549904701201
  30. Buchaille R, Couble ML, Magloire H, Bleicher F : A substractive PCR-based cDNA library from human odontoblast cells: identification of novel genes expressed in tooth forming cells. Matrix Biol, 19:421-430, 2000. https://doi.org/10.1016/S0945-053X(00)00091-3
  31. Nakamura Y, Hammarstrom L, Matsumoto K, Lyngstadaas SP : The induction of reparative dentine by enamel proteins. Int Endod J, 35:407-417, 2002. https://doi.org/10.1046/j.1365-2591.2002.00556.x
  32. Gusman H, Santana RB, Zehnder M : Matrix metalloproteinase levels and gelatinolytic activity in clinically healthy and inflamed human dental pulps. Eur J Oral Sci, 110:353-357, 2002. https://doi.org/10.1034/j.1600-0722.2002.21347.x
  33. Trowbridge HO : Pulp biology: progress during the past 25 years. Aust Endod J, 29:5-12, 2003. https://doi.org/10.1111/j.1747-4477.2003.tb00485.x

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