Skip to main content

Advertisement

SpringerLink
Log in

LncRNA MALAT1 sponges miR-30 to promote osteoblast differentiation of adipose-derived mesenchymal stem cells by promotion of Runx2 expression

  • Regular Article
  • Published:
Cell and Tissue Research Aims and scope Submit manuscript

Abstract

Adipose-derived mesenchymal stem cells (ADSCs) are an important source of stem cells for tissue repair and regeneration but the regulatory mechanism of stem cell differentiation is still unclear. Runt-related gene 2 (Runx2) is a bone-specific transcription factor that plays an important role in promoting osteogenic differentiation. Protein levels of Runx2 are regulated by non-coding RNA. In order to identify the regulatory mechanism underlying non-coding RNA regulation of Runx2, we employed bioinformatics analysis, quantitative reverse transcription PCR (qRT-PCR), osteoblast differentiation induction, immunohistochemical and bifluorescein reporter experiments. The results showed that expression of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and Runx2 was increased in ADSCs induced in osteogenic differentiation media for 21 days, while miR-30 expression was downregulated. qRT-PCR and alkaline phosphatase (ALP) histochemical staining assays demonstrated that knockdown of lncRNA MALAT1 or overexpression of miR-30 suppressed Runx2-mediated osteoblast differentiation by suppressing osteocalcin (OCN), osteopontin (OPN) and osterix (OSX) expression. Overexpressing Runx2 reversed the inhibitory effect of miR-30 on osteogenic differentiation of ADSCs. Bifluorescein report experiments confirmed that miR-30 is a potential target of lncRNA MALAT1 and Runx2 is a potential target of miR-30. Taken together, the results suggested that the expression of lncRNA MALAT1 promoted Runx2-mediated osteogenic differentiation of ADSCs by targeting miR-30.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G (1997) Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 89:747–754

    Article  CAS  PubMed  Google Scholar 

  • Eguchi T, Watanabe K, Hara ES, Ono M, Kuboki T, Calderwood SK (2013) OstemiR: a novel panel of microRNA biomarkers in osteoblastic and osteocytic differentiation from mesencymal stem cells. PLoS One 8:e58796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fernandes M, Valente SG, Sabongi RG, Gomes Dos Santos JB, Leite VM, Ulrich H, Nery AA, da Silva Fernandes MJ (2018) Bone marrow-derived mesenchymal stem cells versus adipose-derived mesenchymal stem cells for peripheral nerve regeneration. Neural Regen Res 13:100–104

    Article  PubMed  PubMed Central  Google Scholar 

  • Gao X, Ge J, Li W, Zhou W, Xu L (2018a) LncRNA KCNQ1OT1 promotes osteogenic differentiation to relieve osteolysis via Wnt/beta-catenin activation. Cell Biosci 8:19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao Y, Xiao F, Wang C, Cui P, Zhang X, Chen X (2018b) Long noncoding RNA MALAT1 promotes osterix expression to regulate osteogenic differentiation by targeting miRNA-143 in human bone marrow-derived mesenchymal stem cells. J Cell Biochem 119:6986–6996

    Article  CAS  PubMed  Google Scholar 

  • Huang G, Kang Y, Huang Z, Zhang Z, Meng F, Chen W, Fu M, Liao W (2017) Identification and characterization of long non-coding RNAs in osteogenic differentiation of human adipose-derived stem cells. Cell Physiol Biochem 42:1037–1050

    Article  CAS  PubMed  Google Scholar 

  • Jin C, Jia L, Huang Y, Zheng Y, Du N, Liu Y, Zhou Y (2016) Inhibition of lncRNA MIR31HG promotes osteogenic differentiation of human adipose-derived stem cells. Stem Cells 34:2707–2720

    Article  CAS  PubMed  Google Scholar 

  • Komori T (2002) Runx2, a multifunctional transcription factor in skeletal development. J Cell Biochem 87:1–8

    Article  CAS  PubMed  Google Scholar 

  • Liu L, Wang J, Song X, Zhu Q, Shen S, Zhang W (2018) Semaphorin 3A promotes osteogenic differentiation in human alveolar bone marrow mesenchymal stem cells. Exp Ther Med 15:3489–3494

    CAS  PubMed  PubMed Central  Google Scholar 

  • Madhurakkat Perikamana SK, Lee J, Ahmad T, Kim EM, Byun H, Lee S, Shin H (2018) Harnessing biochemical and structural cues for tenogenic differentiation of adipose derived stem cells (ADSCs) and development of an in vitro tissue interface mimicking tendon-bone insertion graft. Biomaterials 165:79–93

    Article  CAS  PubMed  Google Scholar 

  • Niu G, Zhuang H, Li B, Cao G (2018) Long noncoding RNA linc-UBC1 promotes tumor invasion and metastasis by regulating EZH2 and repressing E-cadherin in esophageal squamous cell carcinoma. J BUON 23:157–162

    PubMed  Google Scholar 

  • Peng S, Cao L, He S, Zhong Y, Ma H, Zhang Y, Shuai C (2018) An overview of long noncoding RNAs involved in bone regeneration from mesenchymal stem cells. Stem Cells Int 2018:8273648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Su X, Liao L, Shuai Y, Jing H, Liu S, Zhou H, Liu Y, Jin Y (2015) MiR-26a functions oppositely in osteogenic differentiation of BMSCs and ADSCs depending on distinct activation and roles of Wnt and BMP signaling pathway. Cell Death Dis 6:e1851

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun M, Chi G, Li P, Lv S, Xu J, Xu Z, Xia Y, Tan Y, Li L, Li Y (2018) Effects of matrix stiffness on the morphology, adhesion, proliferation and osteogenic differentiation of mesenchymal stem cells. Int J Med Sci 15:257–268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tian Y, Liu J, Bai X, Tan X, Cao Y, Qin K, Zhao Z, Zhang Y (2015) MicroRNA expression profile of surgical removed mandibular bone tissues from patients with mandibular prognathism. J Surg Res 198:127–134

    Article  CAS  PubMed  Google Scholar 

  • Wu T, Zhou H, Hong Y, Li J, Jiang X, Huang H (2012) miR-30 family members negatively regulate osteoblast differentiation. J Biol Chem 287:7503–7511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiao X, Zhou T, Guo S, Guo C, Zhang Q, Dong N, Wang Y (2017) LncRNA MALAT1 sponges miR-204 to promote osteoblast differentiation of human aortic valve interstitial cells through up-regulating Smad4. Int J Cardiol 243:404–412

    Article  PubMed  Google Scholar 

  • Yang Q, Jia L, Li X, Guo R, Huang Y, Zheng Y, Li W (2018) Long noncoding RNAs: new players in the osteogenic differentiation of bone marrow- and adipose-derived mesenchymal stem cells. Stem Cell Rev 14:297–308

    Article  CAS  Google Scholar 

  • Zhang P, Luo X, Wang H (2009) Clinical transplantation of a tissue-engineered airway. Lancet 373:718 author reply 718-719

    Article  PubMed  Google Scholar 

  • Zhang R, Weng Y, Li B, Jiang Y, Yan S, He F, Chen X, Deng F, Wang J, Shi Q (2015) BMP9-induced osteogenic differentiation is partially inhibited by miR-30a in the mesenchymal stem cell line C3H10T1/2. J Mol Histol 46:399–407

    Article  CAS  PubMed  Google Scholar 

  • Zhao J, Zhang C, Gao Z, Wu H, Gu R, Jiang R (2018) Long non-coding RNA ASBEL promotes osteosarcoma cell proliferation, migration, and invasion by regulating microRNA-21. J Cell Biochem 119:6461–6469

    Article  CAS  PubMed  Google Scholar 

  • Zhu Y, Wu Y, Cheng J, Wang Q, Li Z, Wang Y, Wang D, Wang H, Zhang W, Ye J, Jiang H, Wang L (2018) Pharmacological activation of TAZ enhances osteogenic differentiation and bone formation of adipose-derived stem cells. Stem Cell Res Ther 9:53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopaedics, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai, 200032, People’s Republic of China

    Jiayong Yi, Dong Liu & Jian Xiao

Authors
  1. Jiayong Yi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jian Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jian Xiao.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Highlights

1. The expression of lncRNA MALAT1 promoted osteogenic differentiation of ADSCs.

2. The expression of miR-30 suppressed osteogenic differentiation of ADSCs.

3. The miR-30 is a potential target of lncRNA MALAT1.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yi, J., Liu, D. & Xiao, J. LncRNA MALAT1 sponges miR-30 to promote osteoblast differentiation of adipose-derived mesenchymal stem cells by promotion of Runx2 expression. Cell Tissue Res 376, 113–121 (2019). https://doi.org/10.1007/s00441-018-2963-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00441-018-2963-2

Keywords

Search

Navigation