SpringerLink
Log in

MicroRNA-338-3p promotes differentiation of mDPC6T into odontoblast-like cells by targeting Runx2

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Odontoblasts are terminally differentiated cells that play a vital role in dentinogenesis. The differentiation of odontoblasts is regulated by a variety of genetic and epigenetic mechanisms. Our previous microRNA microarray studies verified that miR-338-3p was up-regulated during odontoblast differentiation. The purpose of this study was to determine the function of miR-338-3p during odontoblast differentiation. The upregulation of miR-338-3p expression during odontoblast differentiation was validated by qRT-PCR. Odontoblast differentiation was enhanced after over-expression of miR-338-3p, while a loss of function approach using a miR-338-3p inhibitor impaired odontoblast differentiation. Bioinformatic analysis identified Runx2 as a potential target of miR-338-3p. Overexpression of miR-338-3p caused a decreased in the expression of Runx2 at both mRNA and protein levels, while Runx2 expression increased after treatment with miR-338-3p inhibitors. Furthermore, the activity of a luciferase reporter plasmid containing the 3′-UTR of Runx2 was significantly suppressed by ectopic expression of miR-338-3p. These results suggested that miR-338-3p promotes odontoblast differentiation through targeting Runx2.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ruch JV (1998) Odontoblast commitment and differentiation. Biochem Cell Biol 76:923–938

    Article  CAS  PubMed  Google Scholar 

  2. Tziafas D (1995) Basic mechanisms of cytodifferentiation and dentinogenesis during dental pulp repair. Int J Dev Biol 39:281–290

    CAS  PubMed  Google Scholar 

  3. Arana-Chavez VE, Massa LF (2004) Odontoblasts: the cells forming and maintaining dentine. Int J Biochem Cell Biol 36:1367–1373

    Article  CAS  PubMed  Google Scholar 

  4. Lin H, Xu L, Liu H, Sun Q, Chen Z, Yuan G, Chen Z (2011) KLF4 promotes the odontoblastic differentiation of human dental pulp cells. J Endod 37:948–954

    Article  PubMed  Google Scholar 

  5. Mitsiadis TA, Rahiotis C (2004) Parallels between tooth development and repair: conserved molecular mechanisms following carious and dental injury. J Dent Res 83:896–902

    Article  CAS  PubMed  Google Scholar 

  6. Hardcastle Z, Mo R, Hui CC, Sharpe PT (1998) The Shh signalling pathway in tooth development: defects in Gli2 and Gli3 mutants. Development 125:2803–2811

    CAS  PubMed  Google Scholar 

  7. Michon F, Tummers M, Kyyronen M, Frilander MJ, Thesleff I (2010) Tooth morphogenesis and ameloblast differentiation are regulated by micro-RNAs. Dev Biol 340:355–368

    Article  CAS  PubMed  Google Scholar 

  8. Thesleff I (2003) Epithelial-mesenchymal signalling regulating tooth morphogenesis. J Cell Sci 116:1647–1648

    Article  CAS  PubMed  Google Scholar 

  9. Tummers M, Thesleff I (2009) The importance of signal pathway modulation in all aspects of tooth development. J Exp Zool B 312:309–319

    Article  Google Scholar 

  10. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  CAS  PubMed  Google Scholar 

  11. Mizuno Y, Tokuzawa Y, Ninomiya Y, Yagi K, Yatsuka-Kanesaki Y, Suda T, Fukuda T, Katagiri T, Kondoh Y, Amemiya T, Tashiro H, Okazaki Y (2009) miR-210 promotes osteoblastic differentiation through inhibition of AcvR1b. FEBS Lett 583:2263–2268

    Article  CAS  PubMed  Google Scholar 

  12. Kim D, Song J, Kim S, Chun CH, ** EJ (2011) MicroRNA-34a regulates migration of chondroblast and IL-1beta-induced degeneration of chondrocytes by targeting EphA5. Biochem Biophys Res Commun 415:551–557

    Article  CAS  PubMed  Google Scholar 

  13. Kim YJ, Bae SW, Yu SS, Bae YC, Jung JS (2009) miR-196a regulates proliferation and osteogenic differentiation in mesenchymal stem cells derived from human adipose tissue. J Bone Miner Res 24:816–825

    Article  CAS  PubMed  Google Scholar 

  14. Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A (2005) Identification of mammalian microRNA host genes and transcription units. Genome Res 14:1902–1910

    Article  Google Scholar 

  15. Tsuchiya S, Oku M, Imanaka Y, Kunimoto R, Okuno Y, Terasawa K, Sato F, Tsujimoto G, Shimizu K (2009) MicroRNA-338-3p and microRNA-451 contribute to the formation of basolateral polarity in epithelial cells. Nucleic Acids Res 37:3821–3827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kos A, Olde Loohuis NF, Wieczorek ML, Glennon JC, Martens GJ, Kolk SM, Aschrafi A (2012) A potential regulatory role for intronic microRNA-338-3p for its host gene encoding apoptosis-associated tyrosine kinase. PLoS ONE 7:e31022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Gaur T, Lengner CJ, Hovhannisyan H, Bhat RA, Bodine PV, Komm BS, Javed A, Van Wijnen AJ, Stein JL, Stein GS, Lian JB (2005) Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression. J Biol Chem 280:33132–33140

    Article  CAS  PubMed  Google Scholar 

  18. Huang J, Zhao L, **ng L, Chen D (2010) MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells 28:357–364

    PubMed  PubMed Central  Google Scholar 

  19. Huang X, Xu S, Gao J, Liu F, Yue J, Chen T, Wu B (2011) miRNA expression profiling identifies DSPP regulators in cultured dental pulp cells. Int J Mol Med 28:659–667

    CAS  PubMed  Google Scholar 

  20. Yue J, Wu B, Gao J, Huang X, Li C, Ma D, Fang F (2012) DMP1 is a target of let-7 in dental pulp cells. Int J Mol Med 30:295–301

    CAS  PubMed  Google Scholar 

  21. D’Souza RN, Aberg T, Gaikwad J, Cavender A, Owen M, Karsenty G, Thesleff I (1999) Cbfa1 is required for epithelial-mesenchymal interactions regulating tooth development in mice. Development 126:2911–2920

    PubMed  Google Scholar 

  22. Miyazaki T, Kanatani N, Rokutanda S, Yoshida C, Toyosawa S, Nakamura R, Takada S, Komori T (2008) Inhibition of the terminal differentiation of odontoblasts and their transdifferentiation into osteoblasts in Runx2 transgenic mice. Arch Histol Cytol 71:131–146

    Article  CAS  PubMed  Google Scholar 

  23. Li S, Kong H, Yao N, Yu Q, Wang P, Lin Y, Wang J, Kuang R, Zhao X, Xu J, Zhu Q, Ni L (2011) The role of runt-related transcription factor 2 (Runx2) in the late stage of odontoblast differentiation and dentin formation. Biochem Biophys Res Commun 410:698–704

    Article  CAS  PubMed  Google Scholar 

  24. Li L, Zhu YQ, Jiang L, Peng W, Ritchie HH (2011) Hypoxia promotes mineralization of human dental pulp cells. J Endod 37:799–802

    Article  PubMed  Google Scholar 

  25. Chen S, Rani S, Wu Y, Unterbrink A, Gu TT, Gluhak-Heinrich J, Chuang HH, Macdougall M (2005) Differential regulation of dentin sialophosphoprotein expression by Runx2 during odontoblast cytodifferentiation. J Biol Chem 280:29717–29727

    Article  CAS  PubMed  Google Scholar 

  26. Lewis BP, Burge CB, Bartel DP (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120:15–20

    Article  CAS  PubMed  Google Scholar 

  27. Lee MH, Javed A, Kim HJ, Shin HI, Gutierrez S, Choi JY, Rosen V, Stein JL, van Wijnen AJ, Stein GS, Lian JB, Ryoo HM (1999) Transient upregulation of CBFA1 in response to bone morphogenetic protein-2 and transforming growth factor beta1 in C2C12 myogenic cells coincides with suppression of the myogenic phenotype but is not sufficient for osteoblast differentiation. J Cell Biochem 73:114–125

    Article  CAS  PubMed  Google Scholar 

  28. Doench JG, Petersen CP, Sharp PA (2003) SiRNAs can function as miRNAs. Genes Dev 17:438–442

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zhang ZW, Zhang LQ, Ding L, Wang F, Sun YJ, An Y, Zhao Y, Li YH, Teng CB (2011) MicroRNA-19b downregulates insulin 1 through targeting transcription factor NeuroD1. FEBS Lett 585:2592–2598

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the National 973 project of China (No. 2010CB534915), the National Natural Science Foundation of China (No. 30872880; 81070797), and the PhD Candidates Self-research (Including 1 + 4) Program of Wuhan University in 2011(No. 201130402020007).

Author information

Authors and Affiliations

  1. State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China

    Qin Sun, Huan Liu, Heng Lin, Guohua Yuan, Lu Zhang & Zhi Chen

Authors
  1. Qin Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Huan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Heng Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Guohua Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Zhi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhi Chen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sun, Q., Liu, H., Lin, H. et al. MicroRNA-338-3p promotes differentiation of mDPC6T into odontoblast-like cells by targeting Runx2. Mol Cell Biochem 377, 143–149 (2013). https://doi.org/10.1007/s11010-013-1580-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-013-1580-3

Keywords

Search

Navigation