LncRNA TUG1 promotes osteogenic differentiation of human umbilical cord mesenchymal stem cells by regulating...

This study aims to determine whether long non-coding RNA (lncRNA) taurine up-regulated gene 1 (TUG1) can promote the osteogenic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) by modulating the miR-138/silent information regulator 1 (SIRT1) axis and to explore the underlying mechanisms.

Techniques including flow cytometry, cell staining analysis, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot assay, and dual-luciferase reporter assay were utilized. Osteogenic induction was performed on hUC-MSCs that had undergone passage culture and surface marker characterization, and the level changes of TUG1 were detected. By respectively knocking down or overexpressing TUG1 and miR-138, the effects on osteogenic differentiation of hUC-MSCs were clarified, as well as the interaction between miR-138 and TUG1.Through the knockdown or overexpression of miR-138, the impact of miR-138 on the expression level of SIRT1 was determined. hUC-MSCs were categorized into three groups: the Vector + miR-NC group, the TUG1 + miR-NC group, and the TUG1 + miR-138 mimic group. The expression levels of SIRT1 and osteogenic marker genes were compared across these groups to elucidate the relationship among TUG1, miR-138, and SIRT1 during osteogenic differentiation.

During the osteogenic differentiation of hUC-MSCs, the level of TUG1 increased progressively. The overexpression of TUG1 was capable of facilitating the expression of osteogenic marker genes, accompanied by an increase in the number of mineralized nodules. TUG1 and miR-138 exhibit a reciprocal inhibitory relationship. Moreover, miR-138 shows a negative correlation with both the expression of osteogenic marker genes and the formation of mineralized nodules. SIRT1 serves as a downstream target of miR-138, and its expression is subject to negative regulation by miR-138. Compared with the Vector + miR-NC group, the expression of SIRT1 and osteogenic marker genes was significantly increased in the TUG1 + miR-NC group, while overexpression of miR-138 could counteract the effect of TUG1.

The lncRNA TUG1 promotes the osteogenic differentiation of hUC-MSCs by modulating the miR-138/SIRT1 axis. This molecular mechanism may offer valuable insights for the prevention and treatment of osteoporosis.