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Long non-coding RNA DANCR modulates osteogenic differentiation by regulating the miR-1301-3p/PROX1 axis

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Abstract

The balance of osteoblasts and marrow adipocytes from bone marrow mesenchymal stem cells (BM-MSCs) maintains bone health. Under aging or other pathological stimuli, BM-MSCs will preferentially differentiate into marrow adipocytes and reduce osteoblasts, leading to osteoporosis. Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) participates in the osteogenic differentiation of human BM-MSCs, but the mechanism by which DANCR regulates the osteogenic differentiation of human BM-MSCs has not been fully explained. We observed that DANCR and prospero homeobox 1 (PROX1) were downregulated during osteogenic differentiation of human BM-MSCs, while miR-1301-3p had an opposite trend. DANCR overexpression decreased the levels of alkaline phosphatase, RUNX2, osteocalcin, Osterix in BM-MSCs after osteogenic induction, but DANCR silencing had the opposite result. Moreover, DANCR sponged miR-1301-3p to regulate PROX1 expression. miR-1301-3p overexpression reversed the suppressive role of DANCR elevation on the osteogenic differentiation of human BM-MSCs. Also, PROX1 elevation abolished the promoting role of miR-1301-3p overexpression on the osteogenic differentiation of human BM-MSCs. In conclusion, DANCR suppressed the osteogenic differentiation of human BM-MSCs through the miR-1301-3p/PROX1 axis, offering a novel mechanism by which DANCR is responsible for the osteogenic differentiation of human BM-MSCs.

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Funding

This study was supported by Zhejiang Province Public Welfare Technology Application Research Project (CN), China (Grant No. LGF20H060009).

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Author notes

  1. Wei Weng and Shengdi Di contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopedics, The First People’s Hospital of Huzhou, First Affiliated Hospital of Huzhou University, No. 158 Guangchanghou Road, Huzhou, 313000, China

    Wei Weng, Shitong Xing, Zhengguo Sun, Zheyuan Shen, Xiaojie Dou, Shouyu He, Huibin Tang & Jikang Min

  2. Department of Gynecology, Huzhou Central Hospital, Huzhou Central Hospital of Zhejiang University, Huzhou, 313000, China

    Shengdi Di

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  1. Wei Weng
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Correspondence to Jikang Min.

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Weng, W., Di, S., Xing, S. et al. Long non-coding RNA DANCR modulates osteogenic differentiation by regulating the miR-1301-3p/PROX1 axis. Mol Cell Biochem 476, 2503–2512 (2021). https://doi.org/10.1007/s11010-021-04074-9

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