m6A Regulator-Mediated RNA Methylation Modification Patterns Regulate the Immune Microenvironment in Osteoarthritis

Area of Science:

• Molecular Biology
• Immunology
• Epigenetics
• Osteoarthritis Research

Background:

• Epigenetic regulation, specifically RNA n6 methyl adenosine (m6A) modification, is crucial for immune responses.
• The role of m6A in the osteoarthritis (OA) immune microenvironment is not well understood.
• Investigating m6A regulators offers potential insights into OA pathogenesis and immune modulation.

Purpose of the Study:

• To systematically analyze RNA modification patterns mediated by 23 m6A regulators in osteoarthritis.
• To characterize the m6A-modified immune microenvironment in OA samples.
• To construct a predictive OA m6A nomogram, regulatory networks, and a drug interaction network.

Main Methods:

• Systematic study of RNA modification patterns using 23 m6A regulators across 38 samples.
• Construction of an OA m6A nomogram, m6A-transcription factor-miRNA network, and drug network.
• Validation of key genes (SREBF2, EGR1, YTHDF3, IGF2BP3) and miRNA (hsa-miR-340) expression via RT-qPCR and Western blotting.

Main Results:

• Distinct m6A regulatory factor expression patterns were observed between healthy and OA samples.
• YTHDF3 expression was upregulated in OA, correlating with type II helper cells and TGF-beta receptors.
• Three RNA modification patterns were identified; Mode 3 showed elevated YTHDF3, T helper cells, and TGF-beta receptors, linked to oxidative stress and autophagy pathways. SREBF2, EGR1, YTHDF3, IGF2BP3, and hsa-miR-340 were validated in OA development.

Conclusions:

• m6A modification plays a significant role in shaping the OA immune microenvironment.
• The identified m6A regulators, networks, and validated genes/miRNA provide novel insights into OA pathogenesis.
• The developed OA m6A nomogram can aid in predicting osteoarthritis risk.