母源性表达 8 小核仁 RNA（MEG8）在牙周膜干细胞成骨分化中的作用。

Role of maternally expressed 8 small nucleolar RNA (MEG8) in osteogenic differentiation of periodontal ligament stem cells.

机构信息

Department of Orthodontic, Shanghai Stomatological Hospital, Fudan University, Shanghai, China.

Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai, China.

出版信息

Oral Dis. 2024 Jul;30(5):3351-3362. doi: 10.1111/odi.14759. Epub 2023 Dec 28.

DOI:10.1111/odi.14759

PMID:38155397

Abstract

OBJECTIVES

Periodontal ligament stem cells (PDLSCs) are essential for the treatment of bone diseases because of its great potential to differentiate into osteoblasts. Remarkably, increasing long-non-coding RNAs (lncRNAs) have been reported to be involved in the osteogenic differentiation of PDLSCs. Maternally expressed 8, small nucleolar RNA host gene (MEG8) is implicated in multiple diseases. This study intended to unearth the potential role of MEG8 and unveil the mechanism in PDLSCs undergoing osteoblastic differentiation.

MATERIALS AND METHODS

MEG8 expression was measured by quantitative real-time PCR (RT-qPCR) during osteogenic differentiation of PDLSCs into bone cells. Functional assays were used to uncover the biological function of MEG8. Besides, RNA pulldown, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter assays were used to explore the molecular mechanism of MEG8.

RESULTS

MEG8 was apparently overexpressed in osteogenically differentiated PDLSCs. Moreover, MEG8 deficiency suppressed the osteoblastic differentiation of PDLSCs. Furthermore, MEG8 modulated the expression of transcription factor 4 (TCF4) by scavenging microRNA-495-3p (miR-495-3p) and microRNA-485-3p (miR-485-3p) through the competing endogenous RNA (ceRNA) mechanism, further stimulating the Wnt/β-catenin pathway.

CONCLUSION

MEG8 stimulates the capacity of PDLSCs for osteogenic differentiation through a ceRNA mode.

摘要

目的

牙周膜干细胞（PDLSCs）在骨疾病的治疗中非常重要，因为它具有分化为成骨细胞的巨大潜力。值得注意的是，越来越多的长链非编码 RNA（lncRNA）已被报道参与 PDLSCs 的成骨分化。母系表达 8、小核仁 RNA 宿主基因（MEG8）涉及多种疾病。本研究旨在挖掘 MEG8 的潜在作用，并揭示其在 PDLSCs 成骨分化中的机制。

材料和方法

通过定量实时 PCR（RT-qPCR）测量 PDLSCs 向成骨细胞分化过程中 MEG8 的表达。功能测定用于揭示 MEG8 的生物学功能。此外，使用 RNA 下拉、RNA 结合蛋白免疫沉淀（RIP）和荧光素酶报告基因测定来探索 MEG8 的分子机制。

结果

MEG8 在成骨分化的 PDLSCs 中明显过表达。此外，MEG8 缺乏抑制 PDLSCs 的成骨分化。此外，MEG8 通过清除 microRNA-495-3p（miR-495-3p）和 microRNA-485-3p（miR-485-3p）来调节转录因子 4（TCF4）的表达，通过竞争性内源性 RNA（ceRNA）机制，进一步刺激 Wnt/β-catenin 通路。