METTL3 accelerates staphylococcal protein A (SpA)-induced osteomyelitis progression by regulating m6A...

Area of Science:

• Molecular Biology
• Biochemistry
• Immunology

Background:

• Osteomyelitis (OM) is a bone infection disrupting homeostasis, often caused by Staphylococcus aureus (SA).
• N6-methyladenosine (m6A) regulators are implicated in OM, but their precise role is unclear.
• Methyltransferase-like 3 (METTL3) is a key m6A regulator investigated in this study.

Purpose of the Study:

• To investigate the function of METTL3-mediated m6A modification in osteomyelitis development.
• To elucidate the molecular mechanism involving METTL3, miR-320a, and PIK3CA in SA-induced bone damage.

Main Methods:

• Human bone mesenchymal stem cells (hBMSCs) were treated with staphylococcal protein A (SpA) to model OM.
• METTL3 expression, osteogenic differentiation, oxidative stress, and inflammatory responses were analyzed.
• Functional assays involved METTL3 knockdown, miR-320a mimic, and PIK3CA manipulation.

Main Results:

• METTL3 was upregulated in OM patients and SpA-treated hBMSCs, exacerbating osteogenic inhibition, oxidative stress, and inflammation.
• METTL3 knockdown ameliorated SpA-induced damage, while miR-320a mimic reversed these protective effects.
• The miR-320a/PIK3CA axis was identified as a key downstream pathway regulated by METTL3.

Conclusions:

• The METTL3/m6A/miR-320a/PIK3CA axis plays a critical role in regulating osteogenic differentiation, oxidative stress, and inflammation in OM.
• Targeting the METTL3/m6A pathway offers a potential therapeutic strategy for osteomyelitis.