Unraveling IGFBP3-mediated m6A modification in fracture healing.

Pathol Res Pract

Section Ⅱ, Department of Orthopedics, the 72nd Army Hospital of PLA, Huzhou 313000, P. R. China. Electronic address:

Published: March 2024

Background: This study investigates the role of IGFBP3-mediated m6A modification in regulating the miR-23a-3p/SMAD5 axis and its impact on fracture healing, aiming to provide insights into potential therapeutic targets.

Methods: Utilizing fracture-related datasets, we identified m6A modification-related mRNA and predicted miR-23a-3p as a regulator of SMAD5. We established a mouse fracture healing model and conducted experiments, including Micro-CT, RT-qPCR, Alizarin Red staining, and Alkaline phosphatase (ALP) staining, to assess gene expression and osteogenic differentiation.

Results: IGFBP3 emerged as a crucial player in fracture healing, stabilizing miR-23a-3p through m6A modification, leading to SMAD5 downregulation. This, in turn, inhibited osteogenic differentiation and delayed fracture healing. Inhibition of IGFBP3 partially reversed through SMAD5 inhibition, restoring osteogenic differentiation and fracture healing in vivo.

Conclusion: The IGFBP3/miR-23a-3p/SMAD5 axis plays a pivotal role in fracture healing, highlighting the relevance of m6A modification. IGFBP3's role in stabilizing miR-23a-3p expression through m6A modification offers a potential therapeutic target for enhancing fracture healing outcomes.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2024.155220DOI Listing

Publication Analysis

Top Keywords

fracture healing
32
m6a modification
20
igfbp3-mediated m6a
8
fracture
8
healing
8
potential therapeutic
8
stabilizing mir-23a-3p
8
osteogenic differentiation
8
m6a
6
modification
5

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!