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

  • Mol Cell Biochem. 2021 Jun;476(6):2503-2512. doi: 10.1007/s11010-021-04074-9.
Wei Weng  1 Shengdi Di  2 Shitong Xing  1 Zhengguo Sun  1 Zheyuan Shen  1 Xiaojie Dou  1 Shouyu He  1 Huibin Tang  1 Jikang Min  3
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.
  • 2. Department of Gynecology, Huzhou Central Hospital, Huzhou Central Hospital of Zhejiang University, Huzhou, 313000, China.
  • 3. Department of Orthopedics, The First People's Hospital of Huzhou, First Affiliated Hospital of Huzhou University, No. 158 Guangchanghou Road, Huzhou, 313000, China. [email protected].
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.

Keywords
BM-MSCs; DANCR; OP; PROX1; miR-1301-3p.
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