Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China.
Mol Med Rep. 2013 Feb;7(2):689-93. doi: 10.3892/mmr.2012.1207. Epub 2012 Nov 28.
Canonical Wnt signaling is critical for the control of osteoblast differentiation in human mesenchymal stem cells. MicroRNAs (miRs) are essential regulators of cell differentiation by post‑transcriptional regulation of target gene expression. The aim of the present study was to investigate the molecular mechanism by which miR‑142‑3p promotes osteoblastic differentiation using the human fetal osteoblastic 1.19 (hFOB1.19), real-time PCR and western blot analysis. Results showed an increased expression of miR‑142‑3p during osteoblast differentiation in the mesenchymal precursor cell line, hFOB1.19. In addition, the ectopic over-expression of miR‑142‑3p promoted hFOB1.19 differentiation, whereas the inhibition of miR‑142‑3p repressed differentiation. The expression of miR‑142‑3p was positively correlated with β‑catenin, an important protein in Wnt signaling. The adenomatous polyposis coli (APC) gene was a direct target of miR‑142‑3p, whereby miR‑142‑3p promoted Wnt signaling through inhibition of APC, leading to accumulation and nuclear translocation of β‑catenin. Therefore, miR‑142‑3p may be an essential mediator of osteoblast differentiation and a new therapeutic strategy for osteogenesis disorders.
经典 Wnt 信号通路对于控制人骨髓间充质干细胞中的成骨细胞分化至关重要。microRNAs（miRs）通过靶基因表达的转录后调控，是细胞分化的重要调节因子。本研究旨在探讨 miR-142-3p 通过何种分子机制促进成骨细胞分化，采用人胚成骨细胞 1.19（hFOB1.19），通过实时 PCR 和 Western blot 分析进行研究。结果显示，在间充质前体细胞系 hFOB1.19 中，成骨细胞分化过程中 miR-142-3p 的表达增加。此外，miR-142-3p 的异位过表达促进了 hFOB1.19 分化，而 miR-142-3p 的抑制则抑制了分化。miR-142-3p 的表达与 Wnt 信号通路中的重要蛋白β-连环蛋白呈正相关。腺瘤性结肠息肉病（APC）基因是 miR-142-3p 的直接靶标，miR-142-3p 通过抑制 APC 促进 Wnt 信号通路，导致β-连环蛋白的积累和核转位。因此，miR-142-3p 可能是成骨细胞分化的重要介体，也是成骨障碍的新治疗策略。
