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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 Dis. 2019 Aug 5;10(8):581.

PMID: 31378783

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR42416083 PRMT3 human PRMT3 human Price
IAR4245160 SGC707 SGC707 Price
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