PRMT1-mediated arginine methylation promotes postnatal calvaria bone formation through BMP-Smad signaling

PRMT1 deficiency leads to severely compromised craniofacial development in neural crest cells and profound abnormalities of the craniofacial tissues. Here, we show PRMT1 controls several key processes in calvarial development, including frontal and parietal bone growth rate and the boundary between sutural and osteogenic cells. Pharmacologic PRMT1 inhibition suppresses MC3T3-E1 cell viability and proliferation and impairs osteogenic differentiation. In this text, we investigate the cellular events behind the morphological changes and uncover an essential role of PRMT1 in simulating postnatal bone formation. Inhibition of PRMT1 alleviated BMP signaling through Smads phosphorylation and reduced the deposition of the H4R3me2a mark. Our study demonstrates a regulatory mechanism whereby PRMT1 regulates BMP signaling and the overall properties of the calvaria bone through Smads methylation, which may facilitate the development of an effective therapeutic strategy for craniosynostosis. [Display omitted] •PRMT1 deficient mice exhibit shrink calvaria bone and incomplete suture closure.•PRMT1 ablation impairs pre-osteoblasts proliferation and differentiation.•PRMT1 mediates osteogenesis through Smad phosphorylation and H3K4me2a methylation.•PRMT1 affects the cell cycle of pre-osteoblasts in early osteogenesis.