Asymmetrical methyltransferase PRMT3 regulates human mesenchymal stem cell osteogenesis via miR-3648.

Zhang Min, Liu Xiaomeng, Li Zheng, Du Yangge, Liu Xuejiao, Lv Longwei, Zhang Xiao, Liu Yunsong, Zhang Ping, Zhou Yongsheng

Cell death & disease 2019 Aug 05

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Histone arginine methylation, which is catalyzed by protein arginine methyltransferases (PRMTs), plays a key regulatory role in various biological processes. Several PRMTs are involved in skeletal development; however, their role in the osteogenic differentiation of mesenchymal stem cells (MSCs) is not completely clear. In this study, we aimed to elucidate the function of PRMT3, a type-I PRMT that catalyzes the formation of ω-mono- or asymmetric dimethyl arginine, in MSCs osteogenesis. We found that PRMT3 promoted MSCs osteogenic commitment and bone remodeling. PRMT3 activated the expression of miR-3648 by enhancing histone H4 arginine 3 asymmetric dimethylation (H4R3me2a) levels at promoter region of the gene. Overexpression of miR-3648 rescued impaired osteogenesis in PRMT3-deficient cells. Moreover, administration of Prmt3 shRNA or a chemical inhibitor of PRMT3 (SGC707) caused an osteopenia phenotype in mice. These results indicate that PRMT3 is a potential therapeutic target for the treatment of bone regeneration and osteopenia disorders.

Citation

Zhang Min, Liu Xiaomeng, Li Zheng, Du Yangge, Liu Xuejiao, Lv Longwei, Zhang Xiao, Liu Yunsong, Zhang Ping, Zhou Yongsheng. Asymmetrical methyltransferase PRMT3 regulates human mesenchymal stem cell osteogenesis via miR-3648. Cell death & disease. 2019 Aug 05;10(8):581