Department of Orthopedics, The First People's Hospital of Huzhou, First Affiliated Hospital of Huzhou University, No. 158 Guangchanghou Road, Huzhou, 313000, China.
Department of Gynecology, Huzhou Central Hospital, Huzhou Central Hospital of Zhejiang University, Huzhou, 313000, China.
Mol Cell Biochem. 2021 Jun;476(6):2503-2512. doi: 10.1007/s11010-021-04074-9. Epub 2021 Feb 24.
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.
成骨细胞和骨髓间充质干细胞（BM-MSCs）中的骨髓脂肪细胞之间的平衡维持着骨骼健康。在衰老或其他病理刺激下，BM-MSCs 会优先分化为骨髓脂肪细胞，减少成骨细胞，导致骨质疏松症。长链非编码 RNA 分化拮抗非编码 RNA（DANCR）参与了人 BM-MSCs 的成骨分化，但 DANCR 调节人 BM-MSCs 成骨分化的机制尚未完全阐明。我们观察到，在人 BM-MSCs 的成骨分化过程中，DANCR 和同源盒蛋白 1（PROX1）下调，而 miR-1301-3p 则呈现相反的趋势。DANCR 的过表达降低了成骨诱导后 BM-MSCs 中碱性磷酸酶、RUNX2、骨钙素、Osterix 的水平，但 DANCR 沉默则有相反的结果。此外，DANCR 海绵吸附 miR-1301-3p 以调节 PROX1 的表达。miR-1301-3p 的过表达逆转了 DANCR 升高对人 BM-MSCs 成骨分化的抑制作用。同样，PROX1 的升高消除了 miR-1301-3p 过表达对人 BM-MSCs 成骨分化的促进作用。总之，DANCR 通过 miR-1301-3p/PROX1 轴抑制人 BM-MSCs 的成骨分化，为 DANCR 负责人 BM-MSCs 成骨分化提供了一个新的机制。
