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Long non-coding RNA MEG3 inhibits adipogenesis and promotes osteogenesis of human adipose-derived mesenchymal stem cells via miR-140-5p

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Abstract

lncRNAs are an emerging class of regulators involved in multiple biological processes. MEG3, an lncRNA, acts as a tumor suppressor, has been reported to be linked with osteogenic differentiation of MSCs. However, limited knowledge is available concerning the roles of MEG3 in the multilineage differentiation of hASCs. The current study demonstrated that MEG3 was downregulated during adipogenesis and upregulated during osteogenesis of hASCs. Further functional analysis showed that knockdown of MEG3 promoted adipogenic differentiation, whereas inhibited osteogenic differentiation of hASCs. Mechanically, MEG3 may execute its role via regulating miR-140-5p. Moreover, miR-140-5p was upregulated during adipogenesis and downregulated during osteogenesis in hASCs, which was negatively correlated with MEG3. In conclusion, MEG3 participated in the balance of adipogenic and osteogenic differentiation of hASCs, and the mechanism may be through regulating miR-140-5p.

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Abbreviations

lncRNA:

Long non-coding RNA

MSCs:

Mesenchymal stem cells

hASCs:

Human adipose-derived stem cells

MEG3 :

Maternally expressed gene 3

ncRNA:

Non-coding RNA

miRNA:

microRNA

BMP2 :

Bone morphogenetic protein 2

BMP4 :

Bone morphogenetic protein 4

ALP:

Alkaline phosphatase

ARS:

Alizarin red staining

OCN :

Osteocalcin

RUNX2 :

Runt-related transcription factor 2

CEBP/α :

CCAAT–enhancer-binding proteins-α

TGFβ :

Transforming growth factor β

PPARγ :

Peroxisome proliferator-activated receptor-γ

GAPDH :

Glyceraldehyde 3-phosphate dehydrogenase

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Author contributions

ZL and CJ: performed the experiments and wrote the paper; SC, YZ, and YH: revised the paper, collection and assembly of the data; LJ and WG: conception and design, financial support, and final approval of the manuscript. YZ: financial support, revised the paper, and final approval of the manuscript.

Funding

This study was financially supported by grants from the National Natural Science Foundation of China (81371118, 81200763, 81670963), the Ph.D. Programs Foundation of Ministry of Education of China (20130001110101), the Project for Culturing Leading Talents in Scientific and Technological Innovation of Beijing (Z171100001117169), and the grant of Peking University School and Hospital of Stomatology (PKUSS20140104).

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    Authors and Affiliations

    1. Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China

      Zheng Li, Chanyuan Jin, Si Chen & Yongsheng Zhou

    2. Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, China

      Yunfei Zheng & Yiping Huang

    3. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, 100081, China

      Lingfei Jia

    4. Central Laboratory, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian District, Beijing, 100081, China

      Lingfei Jia

    5. Department of General Dentistry 2, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China

      Wenshu Ge

    6. Beijing Key Laboratory of Digital Stomatology, National Engineering Lab for Digital and Material Technology of Stomatology, Beijing, 100081, China

      Wenshu Ge & Yongsheng Zhou

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    1. Zheng Li
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    Zheng Li and Chanyuan Jin have contributed equally to this article.

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    11010_2017_3015_MOESM1_ESM.tif

    Supplementary Fig. 1 (a) Micrographs of GFP-positive hASCs under ordinary and fluorescent light in hASCs transfected with miR-140-5p, anti-miR-140-5p, and the scrambled vectors (miR-NC, anti-NC). Scale bar: 500 μm (b) H&E staining, Masson’s trichrome staining in the sh-MEG3 and NC groups. Scale bar: 50 μm. Data are shown as the mean ± SD (*P < 0.05). (TIF 10510 KB)

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    Li, Z., Jin, C., Chen, S. et al. Long non-coding RNA MEG3 inhibits adipogenesis and promotes osteogenesis of human adipose-derived mesenchymal stem cells via miR-140-5p. Mol Cell Biochem 433, 51–60 (2017). https://doi.org/10.1007/s11010-017-3015-z

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