Fig. 2

Roles of the lncRNA H19 in osteogenic differentiation. H19 regulates the osteogenesis of MSCs through different regulatory mechanisms, including classical mechanisms and signal pathways in the presence or absence of external stimuli. (a) H19 downregulates TGF-β1 through miR-675 and inhibits the phosphorylation of Smad3, suppressing the targeting of HDAC4/5 to the promoter of Runx2. (b) H19, as a precursor of miR-675, produces two mature miRNAs (miR-675-5p and miR-675-3p), which regulate osteogenic differentiation through the Wnt/β-catenin signaling pathway. (c) H19 sponges with miR-22 and miR-141 to promote Wnt/β-catenin/Runx2 expression, thereby enhancing the osteogenic differentiation of MSCs. (d) H19 binds directly to p53 protein, inhibits the activity of downstream targets of p53, and promotes the proliferation of MSCs. (e) The miR-138 sponge, through competitive binding with H19, reduces the inhibition of the PTK2 gene to promote FAK expression and induce the osteogenic differentiation of MSCs