Scholarlink

<p>Non-coding RNAs, including piwi-interacting RNAs (piRNAs), are known to regulate osteogenic differentiation in bone marrow-derived mesenchymal stem cells (BMSCs); their role in mesenchymal stem cells (MSCs) from diverse origins remains unclear. In this study, we identified piR48444 as a key regulator that is downregulated during the osteogenic differentiation of stem cells from exfoliated deciduous teeth (SHED) but is upregulated in inflamed and aged BMSCs. Functionally, piR48444 inhibited, while its knockdown enhanced osteogenic differentiation across MSCs from multiple sources. Notably, piR48444-depleted MSCs exhibited superior bone defect repair capacity. PiR48444 antagomir promoted bone regeneration in LPS-induced osteolysis mice and aging mice. Mechanistically, we demonstrated that piR48444 targets <i>METTL7A</i>, suppressing <i>BMP2</i> mRNA m<sup>6</sup>A methylation. Furthermore, we discovered that the METTL7A/eIF4E complex binds to BMP2 mRNA, thereby enhancing its translational efficiency. Our findings establish piR48444 as a negative regulator of MSC osteogenesis through METTL7A-mediated <i>BMP2</i> m<sup>6</sup>A methylation, highlighting its potential as a therapeutic target to enhance MSC-based bone regeneration strategies.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

PiR48444 inhibits MSC osteogenic differentiation and bone regeneration via targeting METTL7A/eIF4E-mediated BMP2 m6A methylation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月29日

查看全文
  • Zhichao Zheng,
  • Xingyang Li,
  • Wenguang Qin,
  • Shuiqing Yu,
  • Tianru Xu,
  • Haoyu Cheng,
  • Wei Xie,
  • Zhihe Fu,
  • Guokai Pan,
  • Yuhui Zhang,
  • Wenyan Huang,
  • Fei Liu,
  • Yifan Jiang,
  • Richard T. Jaspers,
  • Janak L. Pathak,
  • Lihong Wu

摘要

Non-coding RNAs, including piwi-interacting RNAs (piRNAs), are known to regulate osteogenic differentiation in bone marrow-derived mesenchymal stem cells (BMSCs); their role in mesenchymal stem cells (MSCs) from diverse origins remains unclear. In this study, we identified piR48444 as a key regulator that is downregulated during the osteogenic differentiation of stem cells from exfoliated deciduous teeth (SHED) but is upregulated in inflamed and aged BMSCs. Functionally, piR48444 inhibited, while its knockdown enhanced osteogenic differentiation across MSCs from multiple sources. Notably, piR48444-depleted MSCs exhibited superior bone defect repair capacity. PiR48444 antagomir promoted bone regeneration in LPS-induced osteolysis mice and aging mice. Mechanistically, we demonstrated that piR48444 targets METTL7A, suppressing BMP2 mRNA m6A methylation. Furthermore, we discovered that the METTL7A/eIF4E complex binds to BMP2 mRNA, thereby enhancing its translational efficiency. Our findings establish piR48444 as a negative regulator of MSC osteogenesis through METTL7A-mediated BMP2 m6A methylation, highlighting its potential as a therapeutic target to enhance MSC-based bone regeneration strategies.