Comparison of long non‑coding RNA expression profiles in human dental follicle cells and human periodontal ligament cells

Wu,Liping; Deng,Lidi; Hong,Hong; Peng,Caixia; Zhang,Xueqin; Chen,Zhengyuan; Ling,Junqi

doi:10.3892/mmr.2019.10308

Comparison of long non‑coding RNA expression profiles in human dental follicle cells and human periodontal ligament cells

Authors:
- Liping Wu
- Lidi Deng
- Hong Hong
- Caixia Peng
- Xueqin Zhang
- Zhengyuan Chen
- Junqi Ling
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Affiliations: Department of Orthodontics, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China, Zhujiang New Town Dental Clinic, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China, Department of Endodontics, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‑Sen University, Guangzhou, Guangdong 510055, P.R. China
Published online on: May 29, 2019 https://doi.org/10.3892/mmr.2019.10308
Pages: 939-950
Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The dental follicle develops into the periodontal ligament, cementum and alveolar bone. Human dental follicle cells (hDFCs) are the precursor cells of periodontal development. Long non‑coding RNAs (lncRNAs) have been revealed to be crucial factors that regulate a variety of biological processes; however, whether lncRNAs serve a role in human periodontal development remains unknown. Therefore, the present study used microarrays to detect the differentially expressed lncRNAs and mRNAs between hDFCs and human periodontal ligament cells (hPDLCs). A total of 845 lncRNAs and 1,012 mRNAs were identified to be differentially expressed in hDFCs and hPDLCs (fold change >2.0 or <‑2.0; P<0.05). Microarray data were validated by reverse transcription‑quantitative polymerase chain reaction. Bioinformatics analyses, including gene ontology, pathway analysis and coding‑non‑coding gene co‑expression network analysis, were performed to determine the functions of the differentially expressed lncRNAs and mRNAs. Bioinformatics analysis identified that a number of pathways may be associated with periodontal development, including the p53 and calcium signaling pathways. This analysis also revealed a number of lncRNAs, including NR_033932, T152410, ENST00000512129, ENST00000540293, uc021sxs.1 and ENST00000609146, which may serve important roles in the biological process of hDFCs. In addition, the lncRNA termed maternally expressed 3 (MEG3) was identified to be differentially expressed in hDFCs by reverse transcription‑quantitative polymerase chain reaction. The knockdown of MEG3 was associated with a reduction of pluripotency makers in hDFCs. In conclusion, for the first time, to the best of our knowledge, the current study determined the different expression profiles of lncRNAs and mRNAs between hDFCs and hPDLCs. The observations made may provide a solid foundation for further research into the molecular mechanisms of lncRNAs in human periodontal development.

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1	Cho MI and Garant PR: Development and general structure of the periodontium. Periodontol 2000. 24:9–27. 2000. View Article : Google Scholar : PubMed/NCBI
2	Itaya S, Oka K, Ogata K, Tamura S, Kira-Tatsuoka M, Fujiwara N, Otsu K, Tsuruga E, Ozaki M and Harada H: Hertwig's epithelial root sheath cells contribute to formation of periodontal ligament through epithelial-mesenchymal transition by TGF-β. Biomed Res. 38:61–69. 2017. View Article : Google Scholar : PubMed/NCBI
3	Sowmya S, Chennazhi KP, Arzate H, Jayachandran P, Nair SV and Jayakumar R: Periodontal specific differentiation of dental follicle stem cells into osteoblast, fibroblast, and cementoblast. Tissue Eng Part C Methods. 21:1044–1058. 2015. View Article : Google Scholar : PubMed/NCBI
4	Seo BM, Miura M, Gronthos S, Bartold PM, Batouli S, Brahim J, Young M, Robey PG, Wang CY and Shi S: Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet. 364:149–155. 2004. View Article : Google Scholar : PubMed/NCBI
5	Menicanin D, Mrozik KM, Wada N, Marino V, Shi S, Bartold PM and Gronthos S: Periodontal-ligament-derived stem cells exhibit the capacity for long-term survival, self-renewal, and regeneration of multiple tissue types in vivo. Stem Cells Dev. 23:1001–1011. 2014. View Article : Google Scholar : PubMed/NCBI
6	Guo S, Guo W, Ding Y, Gong J, Zou Q, Xie D, Chen Y, Wu Y and Tian W: Comparative study of human dental follicle cell sheets and periodontal ligament cell sheets for periodontal tissue regeneration. Cell Transplant. 22:1061–1073. 2013. View Article : Google Scholar : PubMed/NCBI
7	Kashi K, Henderson L, Bonetti A and Carninci P: Discovery and functional analysis of lncRNAs: Methodologies to investigate an uncharacterized transcriptome. Biochim Biophys Acta. 1859:3–15. 2016. View Article : Google Scholar : PubMed/NCBI
8	Ghosal S, Das S and Chakrabarti J: Long noncoding RNAs: New players in the molecular mechanism for maintenance and differentiation of pluripotent stem cells. Stem Cells Dev. 22:2240–2253. 2013. View Article : Google Scholar : PubMed/NCBI
9	Schmitz SU, Grote P and Herrmann BG: Mechanisms of long noncoding RNA function in development and disease. Cell Mol Life Sci. 73:2491–2509. 2016. View Article : Google Scholar : PubMed/NCBI
10	Aprea J and Calegari F: Long non-coding RNAs in corticogenesis: Deciphering the non-coding code of the brain. EMBO J. 34:2865–2884. 2015. View Article : Google Scholar : PubMed/NCBI
11	Korostowski L, Sedlak N and Engel N: The Kcnq1ot1 long non-coding RNA affects chromatin conformation and expression of Kcnq1, but does not regulate its imprinting in the developing heart. PLoS Genet. 8:e10029562012. View Article : Google Scholar : PubMed/NCBI
12	Lv J, Huang Z, Liu H, Liu H, Cui W, Li B, He H, Guo J, Liu Q, Zhang Y and Wu Q: Identification and characterization of long intergenic non-coding RNAs related to mouse liver development. Mol Genet Genomics. 289:1225–1235. 2014. View Article : Google Scholar : PubMed/NCBI
13	Herriges MJ, Swarr DT, Morley MP, Rathi KS, Peng T, Stewart KM and Morrisey EE: Long noncoding RNAs are spatially correlated with transcription factors and regulate lung development. Genes Dev. 28:1363–1379. 2014. View Article : Google Scholar : PubMed/NCBI
14	Hassan MQ, Tye CE, Stein GS and Lian JB: Non-coding RNAs: Epigenetic regulators of bone development and homeostasis. Bone. 81:746–756. 2015. View Article : Google Scholar : PubMed/NCBI
15	Chen L, Song Z, Huang S, Wang R, Qin W, Guo J and Lin Z: lncRNA DANCR suppresses odontoblast-like differentiation of human dental pulp cells by inhibiting wnt/β-catenin pathway. Cell Tissue Res. 364:309–318. 2016. View Article : Google Scholar : PubMed/NCBI
16	Jia Q, Chen X, Jiang W, Wang W, Guo B and Ni L: The regulatory effects of long noncoding RNA-ANCR on dental tissue-derived stem cells. Stem Cells Int. 2016:31468052016. View Article : Google Scholar : PubMed/NCBI
17	Viale-Bouroncle S, Klingelhöffer C, Ettl T and Morsczeck C: The WNT inhibitor APCDD1 sustains the expression of β-catenin during the osteogenic differentiation of human dental follicle cells. Biochem Biophys Res Commun. 457:314–317. 2015. View Article : Google Scholar : PubMed/NCBI
18	Wei M, Zhang M, Adams A and Duan Y: JNK and AKT/GSK3β signaling pathways converge to regulate periodontal ligament cell survival involving XIAP. Biochem Biophys Res Commun. 448:485–491. 2014. View Article : Google Scholar : PubMed/NCBI
19	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
20	Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, et al: Gene ontology: Tool for the unification of biology. The gene ontology consortium. Nat Genet. 25:25–29. 2000. View Article : Google Scholar : PubMed/NCBI
21	Sellers ZP, Schneider G, Maj M and Ratajczak MZ: Analysis of the paternally-imprinted DLK1-MEG3 and IGF2-H19 tandem gene loci in NT2 embryonal carcinoma cells identifies DLK1 as a potential therapeutic target. Stem Cell Rev. 14:823–836. 2018. View Article : Google Scholar : PubMed/NCBI
22	Peng S, Cao L, He S, Zhong Y, Ma H, Zhang Y and Shuai C: An overview of long noncoding RNAs involved in bone regeneration from mesenchymal stem cells. Stem Cells Int. 2018:82736482018. View Article : Google Scholar : PubMed/NCBI
23	Farzi-Molan A, Babashah S, Bakhshinejad B, Atashi A and Fakhr TM: Down-regulation of the non-coding RNA H19 and its derived miR-675 is concomitant with up-regulation of insulin-like growth factor receptor type 1 during neural-like differentiation of human bone marrow mesenchymal stem cells. Cell Biol Int. 42:940–948. 2018. View Article : Google Scholar : PubMed/NCBI
24	Gu X, Li M, Jin Y, Liu D and Wei F: Identification and integrated analysis of differentially expressed lncRNAs and circRNAs reveal the potential ceRNA networks during PDLSC osteogenic differentiation. BMC Genet. 18:1002017. View Article : Google Scholar : PubMed/NCBI
25	Kunej T, Obsteter J, Pogacar Z, Horvat S and Calin GA: The decalog of long non-coding RNA involvement in cancer diagnosis and monitoring. Crit Rev Clin Lab Sci. 51:344–357. 2014. View Article : Google Scholar : PubMed/NCBI
26	Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E and Chang HY: Long noncoding RNA as modular scaffold of histone modification complexes. Science. 329:689–693. 2010. View Article : Google Scholar : PubMed/NCBI
27	Li P, Zhang G, Li J, Yang R, Chen S, Wu S, Zhang F, Bai Y, Zhao H, Wang Y, et al: Long noncoding RNA RGMB-AS1 indicates a poor prognosis and modulates cell proliferation, migration and invasion in lung adenocarcinoma. PLoS One. 11:e1507902016.
28	Sheng N and Li Y, Qian R and Li Y: The clinical significance and biological function of lncRNA RGMB-AS1 in hepatocellular carcinoma. Biomed Pharmacother. 98:577–584. 2018. View Article : Google Scholar : PubMed/NCBI
29	Choi YH, Kim YJ, Jeong HM, Jin YH, Yeo CY and Lee KY: Akt enhances Runx2 protein stability by regulating Smurf2 function during osteoblast differentiation. FEBS J. 281:3656–3666. 2014. View Article : Google Scholar : PubMed/NCBI
30	David D, Jagadeeshan S, Hariharan R, Nair AS and Pillai RM: Smurf2 E3 ubiquitin ligase modulates proliferation and invasiveness of breast cancer cells in a CNKSR2 dependent manner. Cell Div. 9:22014. View Article : Google Scholar : PubMed/NCBI
31	Li B, Chen P, Qu J, Shi L and Zhuang W, Fu J, Li J, Zhang X, Sun Y and Zhuang W: Activation of LTBP3 gene by a long noncoding RNA (lncRNA) MALAT1 transcript in mesenchymal stem cells from multiple myeloma. J Biol Chem. 289:29365–29375. 2014. View Article : Google Scholar : PubMed/NCBI
32	Sun Z, Yu W, Sanz Navarro M, Sweat M, Eliason S, Sharp T, Liu H, Seidel K, Zhang L, Moreno M, et al: Sox2 and Lef-1 interact with Pitx2 to regulate incisor development and stem cell renewal. Development. 143:4115–4126. 2016. View Article : Google Scholar : PubMed/NCBI
33	Santiago L, Daniels G, Wang D, Deng FM and Lee P: Wnt signaling pathway protein LEF1 in cancer, as a biomarker for prognosis and a target for treatment. Am J Cancer Res. 7:1389–1406. 2017.PubMed/NCBI
34	Kessenbrock K, Wang CY and Werb Z: Matrix metalloproteinases in stem cell regulation and cancer. Matrix Biol. 44-46:184–190. 2015. View Article : Google Scholar : PubMed/NCBI
35	Bunch H: Gene regulation of mammalian long non-coding RNA. Mol Genet Genomics. 293:1–15. 2018. View Article : Google Scholar : PubMed/NCBI
36	Levine AJ and Berger SL: The interplay between epigenetic changes and the p53 protein in stem cells. Genes Dev. 31:1195–1201. 2017. View Article : Google Scholar : PubMed/NCBI
37	Tonelli FM, Santos AK, Gomes DA, da Silva SL, Gomes KN, Ladeira LO and Resende RR: Stem cells and calcium signaling. Adv Exp Med Biol. 740:891–916. 2012. View Article : Google Scholar : PubMed/NCBI
38	Liu Q, Hu CH, Zhou CH, Cui XX, Yang K, Deng C, Xia JJ, Wu Y, Liu LC and Jin Y: DKK1 rescues osteogenic differentiation of mesenchymal stem cells isolated from periodontal ligaments of patients with diabetes mellitus induced periodontitis. Sci Rep. 5:131422015. View Article : Google Scholar : PubMed/NCBI
39	Xiang L, Chen M, He L, Cai B, Du Y, Zhang X, Zhou C, Wang C, Mao JJ and Ling J: Wnt5a regulates dental follicle stem/progenitor cells of the periodontium. Stem Cell Res Ther. 5:1352014. View Article : Google Scholar : PubMed/NCBI
40	Ou L, Fang L, Tang H, Qiao H, Zhang X and Wang Z: Dickkopf Wnt signaling pathway inhibitor 1 regulates the differentiation of mouse embryonic stem cells in vitro and in vivo. Mol Med Rep. 13:720–730. 2016. View Article : Google Scholar : PubMed/NCBI
41	Kikuchi A, Yamamoto H, Sato A and Matsumoto S: Wnt5a: Its signalling, functions and implication in diseases. Acta Physiol (Oxf). 204:17–33. 2012. View Article : Google Scholar : PubMed/NCBI
42	Yu CY and Kuo HC: The trans-spliced long noncoding RNA tsRMST impedes human embryonic stem cell differentiation through WNT5A-mediated inhibition of the epithelial-to-mesenchymal transition. Stem Cells. 34:2052–2062. 2016. View Article : Google Scholar : PubMed/NCBI
43	Liu X, Tan GR, Yu M, Cai X, Zhou Y, Ding H, Xie H, Qu F, Zhang R, Lam CU, et al: The effect of tumour necrosis factor-alpha on periodontal ligament stem cell differentiation and the related signaling pathways. Curr Stem Cell Res Ther. 11:593–602. 2016. View Article : Google Scholar : PubMed/NCBI
44	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 : PubMed/NCBI