LncRNA MEG3 Promotes Osteogenic Differentiation of Tendon Stem Cells Via the MiR-129-5p/TCF4/β-Catenin Axis and Thus Contributes to Trauma-Induced Heterotopic Ossification

Overview

Journal Stem Cell Rev Rep

Publisher Springer

Specialty Cell Biology

Date 2023 Jun 7

PMID 37284914

Authors

Hang Liu

Ziyang Sun

Gang Luo

Yuehao Hu

Hongjiang Ruan

Bing Tu

Juehong Li

Cunyi Fan

Affiliations

Soon will be listed here.

Abstract

Background: Heterotopic ossification (HO) is one of the most intractable conditions following injury to the musculoskeletal system. In recent years, much attention has been paid to the role of lncRNA in musculoskeletal disorders, but its role in HO was still unclear. Therefore, this study attempted to determine the role of lncRNA MEG3 in the formation of post-traumatic HO and further explore the underlying mechanisms.

Results: On the basis of high-throughput sequencing and qPCR validation, elevated expression of the lncRNA MEG3 was shown during traumatic HO formation. Accordingly, in vitro experiments demonstrated that lncRNA MEG3 promoted aberrant osteogenic differentiation of tendon-derived stem cells (TDSCs). Mechanical exploration through RNA pulldown, luciferase reporter gene assay and RNA immunoprecipitation assay identified the direct binding relationship between miR-129-5p and MEG3, or miR-129-5p and TCF4. Further rescue experiments confirmed the miR-129-5p/TCF4/β-catenin axis to be downstream molecular cascade responsible for the osteogenic-motivating effects of MEG3 on the TDSCs. Finally, experiments in a mouse burn/tenotomy model corroborated the promoting effects of MEG3 on the formation of HO through the miR-129-5p/TCF4/β-catenin axis.

Conclusions: Our study demonstrated that the lncRNA MEG3 promoted osteogenic differentiation of TDSCs and thus the formation of heterotopic ossification, which could be a potential therapeutic target.

Citing Articles

Global research trends and hotspots on tendon-derived stem cell: a bibliometric visualization study.

Zhang S, Shang J, Gu Z, Gu X, Wang F, Hu X Front Bioeng Biotechnol. 2024; 11:1327027.

PMID: 38260747 PMC: 10801434. DOI: 10.3389/fbioe.2023.1327027.

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