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Preosteoblast-Enriched Lnc-Evf2 Facilitates Osteogenic Differentiation by Targeting Notch

Han Xia, Yuan Xue

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 lncEvf2 decreases the protein level but not the mRNA levels of Notch2, Notch3, and Hes1, all of which correlate with ontogenesis. 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.