Contribution of various long non-coding RNAs and microRNAs in osteogenic pathways

The contribution of various long non-coding RNAs and microRNAs in osteogenic pathways. Numerous lncRNAs and miRNAs have been shown to engage in different osteogenic pathways including BMP, transforming growth factor-β (TGF-β), and Wnt/β-catenin cascades, leading osteogenic differentiation in BMSCs. The binding between BMP and TGF-β with receptors activates SMAD-dependent and SMAD-independent cascades. SMAD2/3 (R-SMAD) is phosphorylated through the TGF-β SMAD-dependent signaling pathway. R-SMAD (phosphorylated) potentially interacts with SMAD4 and enters the nucleus. Further, R-SMAD and SMAD4 with CBP and P300 co-activators influence RUNX2 expression. Within the nucleus, R-SMAD interacts with HDAC4/5 and inhibits RUNX2 expression. Interestingly, non-phosphorylated R-SMAD is broken down by ubiquitination. Several ncRNAs including lncH19-miR-675 and lncH19-miR-675 positively regulate TGF-β SMAD-dependent pathways while lncHOTAIR-miR-17-5p regulates negatively. Significantly, Smurf1/2 and SMAD6/7 express inhibitory action in the BMP SMAD-dependent cascade (R-SMAD and SMAD1/5/8). Specifically, ncRNAs including lncKCNQ1OT1-miR-320a, lncKCNQ1OT1-miR-214, lncNEAT1-miR-29b-3p, and lncLOC103691336-miR138-5p are associated with BMSC growth and differentiation. Moreover, the SMAD-independent signaling event encourages the phosphorylation of RUNX2, DLX5, and OSX. The phosphorylation of RUNX2, DLX5, and OSX is significantly favored by lncHULC-miR-195, lncH19-miR-188, lncMALAT1-miR-143, and lncMALAT1-miR-34c axes. The Wnt/β-catenin pathway induces osteogenic differentiation in BMSCs through β-catenin transportation into the nucleus and following target gene expression. The Wnt/β-catenin pathway is positively regulated by lncLINC00707-miR-370-3p, lncH19-miR-141, lncHULC-miR-195, lncLINC00707-miR-145, lncLINC-ROR- miR-138, lncFAM83H-AS1-miR-541-3p, and miR-145. In RUNX2, lncXIXT-miRNA-30a-5p, and lncDGCR5-miR-30d-5p are the positive regulators while lncMEG3-miR-133a-3p inhibits RUNX2 expression.

Publication

Differential Expression of Non-Coding RNAs in Stem Cell Development and Therapeutics of Bone Disorders (2023) Anurag Mishra, et al. Cells. 2023 Apr;12(8). Figure: F1. Homo sapiens

Disease mentions