Preosteoblast-enriched lnc-Evf2 facilitates osteogenic differentiation by targeting Notch.
Preosteoblast-enriched lnc-Evf2 facilitates osteogenic differentiation by targeting Notch.
复制标题
富含前成骨细胞的 lnc-Evf2 通过靶向 Notch 促进成骨分化。
DOI：
10.1093/abbs/gmaa156
复制
发表时间：
2021
影响因子：
3.7
通讯作者：
Hong Wei
中科院分区：
文献类型：
--
作者：
Zhang Zhen;Qi Haixia;Xia Han;Liu Qi;Ren Yi;Zhang Kun;Xue Yuan;Hong Wei
韧带骨化（OL）和骨质疏松（OP）是多因素疾病，没有明确的临床生物标志物。已知长链非编码rna （lncRNAs）参与调节发病机制。在这里，我们发现了一个成骨前富集的lnc-Evf2，在黄韧带骨化（OLF）中过表达，在黄韧带骨化（op）中下调表达。在成骨诱导过程中，lnc-Evf2逐渐上调，与成骨标记基因表达增强和基质矿化相关。此外，lnc-Evf2的敲低显著抑制成骨分化标志物的表达，延缓成骨细胞矿化过程，表明该分子参与成骨过程。从机制上讲，我们发现lnc-Evf2的沉默降低了Notch2、Notch3和Hes1的蛋白水平，但没有降低它们的mRNA水平，它们都与成骨相关。综上所述，我们的数据表明lnc-Evf2通过Notch信号促进成骨分化和骨形成，表明lnc-Evf2可能作为OL和OP的新的潜在临床靶点。
Ossification of ligaments (OL) and osteoporosis (OP) are multifactorial disorders without definitive clinical biomarkers. Long non-coding RNAs (lncRNAs) are known to involve in regulating pathogenesis. Here, we have identified a preosteoblast-enriched lnc-Evf2 that was overexpressed in ossified ligamentum flavum (OLF) and down-expressed in OP. lnc-Evf2 is gradually upregulated during osteogenic induction, correlating with the enhanced expression of osteogenic marker genes and matrix mineralization. Moreover, knockdown of lnc-Evf2 significantly inhibits the expression of osteogenic differentiation markers and delays the osteoblastic mineralization process, indicating that this molecule is involved in osteogenesis. Mechanistically, we demonstrated that silencing of lnc-Evf2 decreases the protein level but not the mRNA levels of Notch2, Notch3, and Hes1, all of which correlate with osteogenesis. Taken together, our data demonstrate that lnc-Evf2 promotes osteogenic differentiation and bone formation through the Notch signaling, revealing that lnc-Evf2 may serve as a novel potential clinical target of OL and OP.