Comparison of gene expression profiles between dental pulp and periodontal ligament tissues in humans

Gong,Ai-Xiu; Zhang,Jing-Han; Li,Jing; Wu,Jun; Wang,Lin; Miao,Deng-Shun

doi:10.3892/ijmm.2017.3065

Comparison of gene expression profiles between dental pulp and periodontal ligament tissues in humans

Authors:
- Ai-Xiu Gong
- Jing-Han Zhang
- Jing Li
- Jun Wu
- Lin Wang
- Deng-Shun Miao
View Affiliations

Affiliations: Department of Stomatology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China, Department of Neonatology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China, State Key Laboratory of Reproductive Medicine, The Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Jiangsu Key Laboratory of Oral Diseases, Department of Orthodontics, School of Stomatology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: July 12, 2017 https://doi.org/10.3892/ijmm.2017.3065
Pages: 647-660
Copyright: © Gong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

There are anatomical and functional differences between human dental pulp (DP) and periodontal ligament (PDL). However, the molecular biological differences and function of these tissues are poorly understood. In the present study, we employed a cDNA microarray array to screen for differentially expressed genes (DEGs) between human DP and PDL tissues, and used the online software WebGestalt to perform the functional analysis of the DEGs. In addition, the STRING database and KEGG pathway analysis were applied for interaction network and pathway analysis of the DEGs. DP and PDL samples were obtained from permanent premolars (n=16) extracted for orthodontic purposes. The results of the microarray assay were confirmed by RT-qPCR. The DEGs were found to be significantly associated with the extracellular matrix and focal adhesion. A total of 10 genes were selected to confirm the results. The mRNA levels of integrin alpha 4 (ITGA4), integrin alpha 8 (ITGA8), neurexin 1 (NRXN1) and contactin 1 (CNTN1) were significantly higher in the DP than in the PDL tissues. However, the levels of collagen type XI alpha 1 (COL11A1), aggrecan (ACAN), collagen type VI alpha 1 (COL6A1), chondroadherin (CHAD), laminin gamma 2 (LAMC2) and laminin alpha 3 (LAMA3) were higher in the PDL than in the DP samples. The gene expression profiles provide novel insight into the characterization of DP and PDL tissues, and contribute to our understanding of the potential molecular mechanisms of dental tissue mineralization and regeneration.

View Figures

View References

1	Chang CC, Chang KC, Tsai SJ, Chang HH and Lin CP: Neurogenic differentiation of dental pulp stem cells to neuron-like cells in dopaminergic and motor neuronal inductive media. J Formos Med Assoc. 113:956–965. 2014. View Article : Google Scholar : PubMed/NCBI
2	Volponi AA, Pang Y and Sharpe PT: Stem cell-based biological tooth repair and regeneration. Trends Cell Biol. 20:715–722. 2010. View Article : Google Scholar : PubMed/NCBI
3	Ledesma-Martínez E, Mendoza-Núñez VM and Santiago-Osorio E: Mesenchymal stem cells derived from dental pulp: A review. Stem Cells Int. 2016:47095722016. View Article : Google Scholar : PubMed/NCBI
4	McCulloch CA: Proteomics for the periodontium: Current strategies and future promise. Periodontol 2000. 40:173–183. 2006. View Article : Google Scholar : PubMed/NCBI
5	Kim SH, Kim YS, Lee SY, Kim KH, Lee YM, Kim WK and Lee YK: Gene expression profile in mesenchymal stem cells derived from dental tissues and bone marrow. J Periodontal Implant Sci. 41:192–200. 2011. View Article : Google Scholar : PubMed/NCBI
6	Mrozik KM, Zilm PS, Bagley CJ, Hack S, Hoffmann P, Gronthos S and Bartold PM: Proteomic characterization of mesenchymal stem cell-like populations derived from ovine periodontal ligament, dental pulp, and bone marrow: Analysis of differentially expressed proteins. Stem Cells Dev. 19:1485–1499. 2010. View Article : Google Scholar : PubMed/NCBI
7	Eleuterio E, Trubiani O, Sulpizio M, Di Giuseppe F, Pierdomenico L, Marchisio M, Giancola R, Giammaria G, Miscia S, Caputi S, et al: Proteome of human stem cells from periodontal ligament and dental pulp. PLoS One. 8:e711012013. View Article : Google Scholar : PubMed/NCBI
8	Gronthos S, Mankani M, Brahim J, Robey PG and Shi S: Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA. 97:13625–13630. 2000. View Article : Google Scholar : PubMed/NCBI
9	Seo BM, Miura M, Gronthos S, Bartold PM, Batouli S, Brahim J, Young M, Robey PG, Wang CY and Shi S: Investigation of multi-potent postnatal stem cells from human periodontal ligament. Lancet. 364:149–155. 2004. View Article : Google Scholar : PubMed/NCBI
10	Cha Y, Jeon M, Lee HS, Kim S, Kim SO, Lee JH and Song JS: Effects of in vitro osteogenic induction on in vivo tissue regeneration by dental pulp and periodontal ligament stem cells. J Endod. 41:1462–1468. 2015. View Article : Google Scholar : PubMed/NCBI
11	Yang ZH, Zhang XJ, Dang NN, Ma ZF, Xu L, Wu JJ, Sun YJ, Duan YZ, Lin Z and Jin Y: Apical tooth germ cell-conditioned medium enhances the differentiation of periodontal ligament stem cells into cementum/periodontal ligament-like tissues. J Periodontal Res. 44:199–210. 2009. View Article : Google Scholar
12	Mao JJ and Prockop DJ and Prockop DJ: Stem cells in the face: Tooth regeneration and beyond. Cell Stem Cell. 11:291–301. 2012. View Article : Google Scholar : PubMed/NCBI
13	Han X and 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. View Article : Google Scholar : PubMed/NCBI
14	Lee HS, Lee J, Kim SO, Song JS, Lee JH, Lee SI, Jung HS and Choi BJ: Comparative gene-expression analysis of the dental follicle and periodontal ligament in humans. PLoS One. 8:e842012013. View Article : Google Scholar :
15	Song JS, Hwang DH, Kim SO, Jeon M, Choi BJ, Jung HS, Moon SJ, Park W and Choi HJ: Comparative gene expression analysis of the human periodontal ligament in deciduous and permanent teeth. PLoS One. 8:e612312013. View Article : Google Scholar : PubMed/NCBI
16	Lee SW, Jeon M, Lee HS, Song JS, Son HK, Choi HJ, Jung HS, Moon SJ, Park W and Kim SO: Comparative gene-expression analysis of periodontal ligament and dental pulp in the human permanent teeth. J Korean Acad Pediatr Dent (JKAPD). 43:166–175. 2016. View Article : Google Scholar
17	McLachlan JL, Smith AJ, Bujalska IJ and Cooper PR: Gene expression profiling of pulpal tissue reveals the molecular complexity of dental caries. Biochim Biophys Acta. 1741:271–281. 2005. View Article : Google Scholar : PubMed/NCBI
18	Heikinheimo K, Kurppa KJ, Laiho A, Peltonen S, Berdal A, Bouattour A, Ruhin B, Catón J, Thesleff I, Leivo I, et al: Early dental epithelial transcription factors distinguish ameloblastoma from keratocystic odontogenic tumor. J Dent Res. 94:101–111. 2015. View Article : Google Scholar
19	Heikinheimo K, Jee KJ, Niini T, Aalto Y, Happonen RP, Leivo I and Knuutila S: Gene expression profiling of ameloblastoma and human tooth germ by means of a cDNA microarray. J Dent Res. 81:525–530. 2002. View Article : Google Scholar : PubMed/NCBI
20	Hochberg Y and Benjamini Y: More powerful procedures for multiple significance testing. Stat Med. 9:811–818. 1990. View Article : Google Scholar : PubMed/NCBI
21	Wang J, Duncan D, Shi Z and Zhang B: WEB-based GEne SeT AnaLysis Toolkit (WebGestalt): Update 2013. Nucleic Acids Res. 41:W77–83. 2013. View Article : Google Scholar : PubMed/NCBI
22	Zhang B, Kirov S and Snoddy J: WebGestalt: An integrated system for exploring gene sets in various biological contexts. Nucleic Acids Res. 33:W741–W748. 2005. View Article : Google Scholar : PubMed/NCBI
23	Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A, Lin J, Minguez P, Bork P, von Mering C, et al: STRING v9.1: Protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res. 41:D808–D815. 2013. View Article : Google Scholar :
24	Butler WT, Brunn JC and Qin C: Dentin extracellular matrix (ECM) proteins: Comparison to bone ECM and contribution to dynamics of dentinogenesis. Connect Tissue Res. 44(Suppl 1): 171–178. 2003. View Article : Google Scholar : PubMed/NCBI
25	Butler WT: Dentin extracellular matrix and dentinogenesis. Oper Dent. (Suppl 5): 18–23. 1992.PubMed/NCBI
26	Martowicz A, Seeber A and Untergasser G: The role of EpCAM in physiology and pathology of the epithelium. Histol Histopathol. 31:349–355. 2016.
27	Mohebiany AN, Harroch S and Bouyain S: New insights into the roles of the contactin cell adhesion molecules in neural development. Adv Neurobiol. 8:165–194. 2014. View Article : Google Scholar : PubMed/NCBI
28	Missler M, Zhang W, Rohlmann A, Kattenstroth G, Hammer RE, Gottmann K and Südhof TC: Alpha-neurexins couple Ca²⁺ channels to synaptic vesicle exocytosis. Nature. 423:939–948. 2003. View Article : Google Scholar : PubMed/NCBI
29	Graf ER, Zhang X, Jin SX, Linhoff MW and Craig AM: Neurexins induce differentiation of GABA and glutamate post-synaptic specializations via neuroligins. Cell. 119:1013–1026. 2004. View Article : Google Scholar : PubMed/NCBI
30	Hessle L, Stordalen GA, Wenglén C, Petzold C, Tanner E, Brorson SH, Baekkevold ES, Önnerfjord P, Reinholt FP and Heinegård D: The skeletal phenotype of chondroadherin deficient mice. PLoS One. 8:e630802013. View Article : Google Scholar : PubMed/NCBI
31	Fukumoto S and Yamada Y: Review: Extracellular matrix regulates tooth morphogenesis. Connect Tissue Res. 46:220–226. 2005. View Article : Google Scholar
32	Iwamoto DV and Calderwood DA: Regulation of integrin-mediated adhesions. Curr Opin Cell Biol. 36:41–47. 2015. View Article : Google Scholar : PubMed/NCBI
33	De Franceschi N, Hamidi H, Alanko J, Sahgal P and Ivaska J: Integrin traffic - the update. J Cell Sci. 128:839–852. 2015. View Article : Google Scholar : PubMed/NCBI
34	Zhu Q, Safavi KE and Spångberg LS: Integrin expression in human dental pulp cells and their role in cell attachment on extracellular matrix proteins. J Endod. 24:641–644. 1998. View Article : Google Scholar
35	Degistirici O, Jaquiery C, Schönebeck B, Siemonsmeier J, Götz W, Martin I and Thie M: Defining properties of neural crest-derived progenitor cells from the apex of human developing tooth. Tissue Eng Part A. 14:317–330. 2008. View Article : Google Scholar : PubMed/NCBI
36	Mercurio AM: Laminin receptors: Achieving specificity through cooperation. Trends Cell Biol. 5:419–423. 1995. View Article : Google Scholar : PubMed/NCBI
37	Aota S and Yamada KM: Fibronectin and cell adhesion: Specificity of integrin-ligand interaction. Adv Enzymol Relat Areas Mol Biol. 70:1–21. 1995.PubMed/NCBI
38	Popova SN, Barczyk M, Tiger CF, Beertsen W, Zigrino P, Aszodi A, Miosge N, Forsberg E and Gullberg D: Alpha11 beta1 integrin-dependent regulation of periodontal ligament function in the erupting mouse incisor. Mol Cell Biol. 27:4306–4316. 2007. View Article : Google Scholar : PubMed/NCBI
39	Barczyk M, Bolstad AI and Gullberg D: Role of integrins in the periodontal ligament: Organizers and facilitators. Periodontol 2000. 63:29–47. 2013. View Article : Google Scholar : PubMed/NCBI
40	Chen J, McCulloch CA and Sodek J: Bone sialoprotein in developing porcine dental tissues: Cellular expression and comparison of tissue localization with osteopontin and osteonectin. Arch Oral Biol. 38:241–249. 1993. View Article : Google Scholar : PubMed/NCBI
41	Hannas AR, Pereira JC, Granjeiro JM and Tjäderhane L: The role of matrix metalloproteinases in the oral environment. Acta Odontol Scand. 65:1–13. 2007. View Article : Google Scholar : PubMed/NCBI
42	Beklen A, Al-Samadi A and Konttinen YT: Expression of cathepsin K in periodontitis and in gingival fibroblasts. Oral Dis. 21:163–169. 2015. View Article : Google Scholar
43	Sorsa T, Tjäderhane L, Konttinen YT, Lauhio A, Salo T, Lee HM, Golub LM, Brown DL and Mäntylä P: Matrix metalloproteinases: Contribution to pathogenesis, diagnosis and treatment of periodontal inflammation. Ann Med. 38:306–321. 2006. View Article : Google Scholar : PubMed/NCBI
44	Tang BL: ADAMTS: A novel family of extracellular matrix proteases. Int J Biochem Cell Biol. 33:33–44. 2001. View Article : Google Scholar : PubMed/NCBI
45	Sone S, Nakamura M, Maruya Y, Takahashi I, Mizoguchi I, Mayanagi H and Sasano Y: Expression of versican and ADAMTS during rat tooth eruption. J Mol Histol. 36:281–288. 2005. View Article : Google Scholar : PubMed/NCBI
46	Lim WH, Liu B, Cheng D, Williams BO, Mah SJ and Helms JA: Wnt signaling regulates homeostasis of the periodontal ligament. J Periodontal Res. 49:751–759. 2014. View Article : Google Scholar : PubMed/NCBI
47	Cyster JG, Ansel KM, Reif K, Ekland EH, Hyman PL, Tang HL, Luther SA and Ngo VN: Follicular stromal cells and lymphocyte homing to follicles. Immunol Rev. 176:181–193. 2000. View Article : Google Scholar : PubMed/NCBI
48	Nakajima T, Amanuma R, Ueki-Maruyama K, Oda T, Honda T, Ito H and Yamazaki K: CXCL13 expression and follicular dendritic cells in relation to B-cell infiltration in periodontal disease tissues. J Periodontal Res. 43:635–641. 2008. View Article : Google Scholar : PubMed/NCBI
49	Liu M, Sun Y, Liu Y, Yuan M, Zhang Z and Hu W: Modulation of the differentiation of dental pulp stem cells by different concentrations of β-glycerophosphate. Molecules. 17:1219–1232. 2012. View Article : Google Scholar : PubMed/NCBI
50	Ravindran S and George A: Dentin matrix proteins in bone tissue engineering. Adv Exp Med Biol. 881:129–142. 2015. View Article : Google Scholar : PubMed/NCBI
51	Karlström E, Ek-Rylander B, Wendel M and Andersson G: Isolation and phenotypic characterization of a multinucleated tartrate-resistant acid phosphatase-positive bone marrow macrophage. Exp Hematol. 39:339–350.e3. 2011. View Article : Google Scholar : PubMed/NCBI
52	Arner EC: Aggrecanase-mediated cartilage degradation. Curr Opin Pharmacol. 2:322–329. 2002. View Article : Google Scholar : PubMed/NCBI