TRIB3 Promotes Osteogenic Differentiation of Human Adipose-derived Mesenchymal Stem Cells Levelled by Posttranscriptional Regulation of miR-24-3p.

Autor: Xiang Song BAI, Ping ZHANG, Yun Song LIU, Hao LIU, Long Wei LV, Yong Sheng ZHOU
Předmět:
Zdroj: Chinese Journal of Dental Research; Winter2021, Vol. 24 Issue 4, p235-249, 15p, 1 Diagram, 1 Chart, 6 Graphs
Abstrakt: Objective: To explore the effect of TRIB3 on the osteogenic differentiation of human adiposederived mesenchymal stem cells (hASCs) and reveal the potential role of TRIB3 in bone regeneration. Methods: TRIB3-knockdown and TRIB3-overexpression hASCs were used to explore the effect of TRIB3 on osteogenic differentiation by alkaline phosphatase (ALP) staining, alizarin red S (ARS) staining, quantitative real-time polymerase chain reaction (qRT-PCR) and heterotopic bone formation. The regulation of miR-24-3p on TRIB3 was detected by qRT-PCR and western blot. Ribonucleic acid (RNA) sequencing was performed to investigate the downstream regulatory network of TRIB3. Results: TRIB3 promoted the osteogenic differentiation of hASCs both in vitro and in vivo. This process was regulated epigenetically by the post-transcriptional regulation of miR-24-3p, which could bind directly to the three prime untranslated region (3'UTR) of TRIB3 and inhibit TRIB3 expression. The downstream regulatory network of TRIB3-mediated osteogenic differentiation was related to calcium ion binding and cell metabolism, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and nuclear factor-κB (NF-κB) signalling pathways. Conclusion: TRIB3 is a promising therapeutic target for hASC-based bone tissue engineering and the epigenetic regulation of TRIB3 through miR-24-3p permits regulatory controllability, thus promoting osteogenesis through an important metabolic target while obtaining a safe and controllable effect via post-transcriptional epigenetic regulation. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index