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Cell Tissue Res. 2019 Apr;376(1):113-121. doi: 10.1007/s00441-018-2963-2. Epub 2018 Dec 3.

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

Author information

1
Department of Orthopaedics, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai, 200032, People's Republic of China.
2
Department of Orthopaedics, Zhongshan Hospital, Fudan University, 180 Fenglin Rd, Shanghai, 200032, People's Republic of China. xiao.jian1@zs-hospital.sh.cn.

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.

KEYWORDS:

Adipose-derived mesenchymal stem cells; LncRNA MALAT1; Osteoblast differentiation; Runx2; miR-30

PMID:
30511267
DOI:
10.1007/s00441-018-2963-2

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