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Biosci Rep. 2017 Jul 21;37(4). pii: BSR20170347. doi: 10.1042/BSR20170347. Print 2017 Aug 31.

Long noncoding RNA DANCR regulates miR-1305-Smad 4 axis to promote chondrogenic differentiation of human synovium-derived mesenchymal stem cells.

Author information

1
Department of Orthopedics, Jinling Hospital, Nanjing University, School of Medicine, Nanjing, China.
2
Department of Orthopedics, Nanjing Jiangbei People's Hospital, Nanjing, China.
3
Department of Orthopedics, Nanjing General Hospital, The Second Military Medical University Clinical Medical School of Nanjing, Nanjing, China.
4
Department of Orthopedics, Jinling Hospital, Nanjing University, School of Medicine, Nanjing, China yishengzhouli@qq.com zhaojianningmyc@163.com.

Abstract

miRNAs have been reported to regulate cellular differentiation by modulating multiple signaling pathways. Long noncoding RNA (lnc RNA) DANCR was previously identified to be critical for the chondrogenesis of human synovium-derived mesenchymal stem cells (SMSC), however, the underlying molecular mechanism requires better understanding. Here, miRNA expression profiling in DANCR overexpressed in SMSCs identified significant down-regulation of miR-1305, which serves as a downstream target of DANCR. Notably, miR-1305 overexpression reversed DANCR-induced cell proliferation and chondrogenic differentiation of SMSCs, which suggested that miR-1305 antagonized the function of DANCR. Mechanistically, highly expressed miR-1305 resulted in the decreased expression of the TGF-β pathway member Smad4, and inhibition of miR-1305 enhanced the expression level of Smad4. Depletion of Smad4 suppressed the promotion of DANCR in cell proliferation and chondrogenesis of SMSCs. Collectively, our results characterized miR-1305-Smad4 axis as a major downstream functional mechanism of lncRNA DANCR in promoting the chondrogenesis in SMSCs.

KEYWORDS:

DANCR; SMSC; Smad4; chondrogenesis; miR-1305

PMID:
28674107
PMCID:
PMC5520215
DOI:
10.1042/BSR20170347
[Indexed for MEDLINE]
Free PMC Article

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