Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Orthopedic Surgery, Beijing Jishuitan Hospital, Fourth Clinical College of Peking University, Jishuitan Orthopaedic College of Tsinghua University, Beijing, China.
J Pineal Res. 2019 Apr;66(3):e12558. doi: 10.1111/jpi.12558. Epub 2019 Feb 14.
Congenital spinal deformities are a result of defective somitogenesis and are associated with vitamin A deficiency (VAD). However, the molecular mechanisms of VAD-associated congenital spinal deformities remain largely unknown. Increasing number of studies suggested that microRNAs and melatonin played important roles in the development of congenital spinal deformities. In this study, we showed that the whole-embryo expression of miR-363 was upregulated in VAD rats. Furthermore, we demonstrated that miR-363 inhibited the proliferation and neuronal differentiation of primary cultured NSCs, accompanied by downregulation of Notch1. To this end, melatonin suppressed miR-363 expression and rescued the effects of miR-363 on NSC proliferation and neuronal differentiation together with restoration of Notch signaling. The present study provided new insights into the mechanism of VAD-associated spinal deformities and the therapeutic effect of melatonin that may lead to novel understanding of the molecular mechanisms of congenital spinal deformities.
先天性脊柱畸形是体节形成缺陷的结果，与维生素 A 缺乏症（VAD）有关。然而，VAD 相关先天性脊柱畸形的分子机制在很大程度上仍不清楚。越来越多的研究表明，microRNAs 和褪黑素在先天性脊柱畸形的发育中发挥着重要作用。在本研究中，我们表明 miR-363 的全胚胎表达在 VAD 大鼠中上调。此外，我们证明 miR-363 抑制原代培养神经干细胞的增殖和神经元分化，同时下调 Notch1。为此，褪黑素抑制 miR-363 的表达，并与 Notch 信号的恢复一起挽救 miR-363 对 NSC 增殖和神经元分化的作用。本研究为 VAD 相关脊柱畸形的机制和褪黑素的治疗效果提供了新的见解，这可能导致对先天性脊柱畸形的分子机制的新认识。
