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

Ding Gao1, Jian Shi2, Siyu Lu2

  • 1Department of Orthopedic Trauma Surgery, Meizhou People's Hospital, Meizhou, 514031, China.

Journal of Orthopaedic Surgery and Research
|November 7, 2024
PubMed

Insights

Methyltransferase-like 3 (METTL3) regulates bone homeostasis in osteomyelitis (OM) by controlling the m6A/miR-320a/PIK3CA axis. Silencing METTL3 alleviates OM development by mitigating inflammation and oxidative stress.

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.
Keywords:
staphylococcus aureusInflammatory responseOsteogenic differentiationOsteomyelitisOxidative stress

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