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.

中文翻译：

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富前成骨细胞的lnc-Evf2通过靶向Notch促进成骨分化

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。已知长的非编码RNA（lncRNA）参与调节发病机理。在这里，我们确定了富含前骨母细胞的lnc-Evf2在骨化黄韧带（OLF）中过表达，而在OP中过表达。lnc-Evf2在成骨诱导过程中逐渐上调，与成骨标记基因的表达增强和基质矿化有关。此外，敲低lnc-Evf2会显着抑制成骨分化标志物的表达，并延迟成骨细胞的矿化过程，表明该分子参与成骨过程。从机制上讲，我们证明了沉默lnc-Evf2会降低Notch2，Notch3，和Hes1，所有这些都与成骨有关。两者合计，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可以作为OL和OP的新型潜在临床靶标。