MicroRNA-29c-tetrahedral Framework Nucleic Acids: Towards Osteogenic Differentiation of Mesenchymal Stem Cells and Bone Regeneration in Critical-sized Calvarial Defects

Overview

Journal Cell Prolif

Date 2024 Feb 28

PMID 38414296

Authors

Jiafei Sun

Xingyu Chen

Yunfeng Lin

Xiaoxiao Cai

Affiliations

Soon will be listed here.

Abstract

Certain miRNAs, notably miR29c, demonstrate a remarkable capacity to regulate cellular osteogenic differentiation. However, their application in tissue regeneration is hampered by their inherent instability and susceptibility to degradation. In this study, we developed a novel miR29c delivery system utilising tetrahedral framework nucleic acids (tFNAs), aiming to enhance its stability and endocytosis capability, augment the efficacy of miR29c, foster osteogenesis in bone marrow mesenchymal stem cells (BMSCs), and significantly improve the repair of critical-sized bone defects (CSBDs). We confirmed the successful synthesis and biocompatibility of sticky ends-modified tFNAs (stFNAs) and miR29c-modified stFNAs (stFNAs-miR29c) through polyacrylamide gel electrophoresis, microscopy scanning, a cell counting kit-8 assay and so on. The mechanism and osteogenesis effects of stFNAs-miR29c were explored using immunofluorescence staining, western blotting, and reserve transcription quantitative real-time polymerase chain reaction. Additionally, the impact of stFNAs-miR29c on CSBD repair was assessed via micro-CT and histological staining. The nano-carrier, stFNAs-miR29c was successfully synthesised and exhibited exemplary biocompatibility. This nano-nucleic acid material significantly upregulated osteogenic differentiation-related markers in BMSCs. After 2 months, stFNAs-miR29c demonstrated significant bone regeneration and reconstruction in CSBDs. Mechanistically, stFNAs-miR29c enhanced osteogenesis of BMSCs by upregulating the Wnt signalling pathway, contributing to improved bone tissue regeneration. The development of this novel nucleic acid nano-carrier, stFNAs-miR29c, presents a potential new avenue for guided bone regeneration and bone tissue engineering research.

Citing Articles

Current Understanding and Translational Prospects of Tetrahedral Framework Nucleic Acids.

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MicroRNA-29c-tetrahedral framework nucleic acids: Towards osteogenic differentiation of mesenchymal stem cells and bone regeneration in critical-sized calvarial defects.

Sun J, Chen X, Lin Y, Cai X Cell Prolif. 2024; 57(7):e13624.

PMID: 38414296 PMC: 11216942. DOI: 10.1111/cpr.13624.

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