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

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

School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, China. · pubmed

Paper

Abstract

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 m

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Research summary

The paper claims that piR48444 inhibits osteogenic differentiation and enhances bone regeneration in mesenchymal stem cells. This research is relevant as it explores mechanisms that could potentially influence bone health and regeneration, which are critical aspects of aging and longevity.

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