2. Academic Validation
  3. Role of METTL16 in PPARγ methylation and osteogenic differentiation

Role of METTL16 in PPARγ methylation and osteogenic differentiation

  • Cell Death Dis. 2025 Apr 10;16(1):271. doi: 10.1038/s41419-025-07527-x.
Liangjie Lu 1,  Lijun Wang 2,  Minjie Yang 3,  Huihan Wang 4
Affiliations

Affiliations

  • 1 Department of Orthopedics, Ningbo Medical Center Li Huili Hospital, Li Huili Hospital Affiliated to Ningbo University, Ningbo, China. 2380179@tongji.edu.cn.
  • 2 Department of Pediatrics, The First Hospital of Jilin University, Changchun, China.
  • 3 Department of Orthopaedics, Jiu jiang NO.1 People's Hospital, Jiu jiang, China.
  • 4 Department of Orthopaedics, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
PMID: 40210616 DOI: 10.1038/s41419-025-07527-x
Abstract

Osteoporosis, a prevalent bone disease, is characterized by the deterioration of bone tissue microstructure and imbalanced osteogenesis. The regulatory role of PPARγ m6A methylation mediated by METTL16 remains poorly elucidated. This study utilized advanced single-cell RNA Sequencing (scRNA-seq) and Bulk RNA-seq techniques to explore how METTL16 influences the osteogenic differentiation of Bone Marrow-Derived Mesenchymal Stem Cells (BMSCs) and its implication in osteoporosis. The research revealed that METTL16 enhances the suppression of osteogenic differentiation in BMSCs, while PPARγ is associated with BMSC Ferroptosis. Mechanistically, METTL16 facilitates the m6A modification of PPARγ transcription, thereby promoting Ferroptosis in BMSCs and impeding their osteogenic differentiation. The in vivo animal experiments confirmed the pivotal role of the METTL16-PPARγ axis in osteoporosis development in mice. These findings suggest that the regulation of PPARγ m6A methylation by METTL16, leading to Ferroptosis, is a critical mechanism impacting BMSC osteogenic differentiation and the pathogenesis of osteoporosis.

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