The Mechanism of LncRNA MALAT1 Targeting the MiR-124-3p/IGF2BP1 Axis to Regulate Osteogenic Differentiation of Periodontal Ligament Stem Cells

Overview

Journal Clin Oral Investig

Specialty Dentistry

Date 2024 Mar 16

PMID 38492123

Authors

Nan Gu

Yao Wang

Lingfeng Li

Xin Sui

Zhihui Liu

Affiliations

Soon will be listed here.

Abstract

Objectives: This study aimed to investigate the regulatory roles of lncRNA MALAT1, miR-124-3p, and IGF2BP1 in osteogenic differentiation of periodontal ligament stem cells (PDLSCs).

Materials And Methods: We characterized PDLSCs by employing quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses to evaluate the expression of key osteogenic markers including ALPL, SPP1, and RUNX2. Manipulation of lncRNA MALAT1 and miR-124-3p expression levels was achieved through transfection techniques. In addition, early osteogenic differentiation was assessed via Alkaline phosphatase (ALP) staining, and mineral deposition was quantified using Alizarin Red S (ARS) staining. Cellular localization of lncRNA MALAT1 was determined through Fluorescence In Situ Hybridization (FISH). To elucidate the intricate regulatory network, we conducted dual-luciferase reporter assays to decipher the binding interactions between lncRNA MALAT1 and miR-124-3P as well as between miR-124-3P and IGF2BP1.

Results: Overexpression of lncRNA MALAT1 robustly promoted osteogenesis in PDLSCs, while its knockdown significantly inhibited the process. We confirmed the direct interaction between miR-124-3p and lncRNA MALAT1, underscoring its role in impeding osteogenic differentiation. Notably, IGF2BP1 was identified as a direct binding partner of lncRNA MALAT1, highlighting its pivotal role within this intricate network. Moreover, we determined the optimal IGF2BP1 concentration (50 ng/ml) as a potent enhancer of osteogenesis, effectively countering the inhibition induced by si-MALAT1. Furthermore, in vivo experiments utilizing rat calvarial defects provided compelling evidence, solidifying lncRNA MALAT1's crucial role in bone formation.

Conclusions: Our study reveals the regulatory network involving lncRNA MALAT1, miR-124-3p, and IGF2BP1 in PDLSCs' osteogenic differentiation.

Clinical Relevance: These findings enhance our understanding of lncRNA-mediated osteogenesis, offering potential therapeutic implications for periodontal tissue regeneration and the treatment of bone defects.

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