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.
Hang Liu, Ziyang Sun, Gang Luo, Yuehao Hu, Hongjiang Ruan, Bing Tu, Juehong Li, Cunyi Fan
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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.
期刊介绍：
The purpose of Stem Cell Reviews and Reports is to cover contemporary and emerging areas in stem cell research and regenerative medicine. The journal will consider for publication:
i) solicited or unsolicited reviews of topical areas of stem cell biology that highlight, critique and synthesize recent important findings in the field.
ii) full length and short reports presenting original experimental work.
iii) translational stem cell studies describing results of clinical trials using stem cells as therapeutics.
iv) papers focused on diseases of stem cells.
v) hypothesis and commentary articles as opinion-based pieces in which authors can propose a new theory, interpretation of a controversial area in stem cell biology, or a stem cell biology question or paradigm. These articles contain more speculation than reviews, but they should be based on solid rationale.
vi) protocols as peer-reviewed procedures that provide step-by-step descriptions, outlined in sufficient detail, so that both experts and novices can apply them to their own research.
vii) letters to the editor and correspondence.
In order to facilitate this exchange of scientific information and exciting novel ideas, the journal has created five thematic sections, focusing on:
i) the role of adult stem cells in tissue regeneration;
ii) progress in research on induced pluripotent stem cells, embryonic stem cells and mechanism governing embryogenesis and tissue development;
iii) the role of microenvironment and extracellular microvesicles in directing the fate of stem cells;
iv) mechanisms of stem cell trafficking, stem cell mobilization and homing with special emphasis on hematopoiesis;
v) the role of stem cells in aging processes and cancerogenesis.
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