1. Academic Validation
  2. PRMT1-mediated arginine methylation promotes postnatal calvaria bone formation through BMP-Smad signaling

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

  • Bone. 2023 Aug 25;116887. doi: 10.1016/j.bone.2023.116887.
Huayu Ye 1 Li Cao 2 Olan Jackson-Weaver 3 Leilei Zheng 4 Yongchao Gou 5
Affiliations

Affiliations

  • 1 Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, 426#, Songshi North Road, Yubei District, Chongqing 401147, PR China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, 426#, Songshi North Road, Yubei District, Chongqing 401147, PR China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, 426#, Songshi North Road, Yubei District, Chongqing 401147, PR China. Electronic address: paprika@stu.cqmu.edu.cn.
  • 2 Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, 426#, Songshi North Road, Yubei District, Chongqing 401147, PR China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, 426#, Songshi North Road, Yubei District, Chongqing 401147, PR China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, 426#, Songshi North Road, Yubei District, Chongqing 401147, PR China. Electronic address: 500292@hospital.cqmu.edu.cn.
  • 3 Center for Craniofacial Molecular Biology, School of Dentistry, University of Southern California, Los Angeles, CA, USA; Trauma & Critical Care Education Division, Tulane School of Medicine, Tulane University, New Orleans, LA, USA. Electronic address: ojacksonweaver@tulane.edu.
  • 4 Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, 426#, Songshi North Road, Yubei District, Chongqing 401147, PR China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, 426#, Songshi North Road, Yubei District, Chongqing 401147, PR China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, 426#, Songshi North Road, Yubei District, Chongqing 401147, PR China. Electronic address: zhengleileicqmu@hospital.cqmu.edu.cn.
  • 5 Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, 426#, Songshi North Road, Yubei District, Chongqing 401147, PR China; Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, 426#, Songshi North Road, Yubei District, Chongqing 401147, PR China; Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, 426#, Songshi North Road, Yubei District, Chongqing 401147, PR China. Electronic address: 501294@hospital.cqmu.edu.cn.
Abstract

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.

Keywords

Cell differentiation; Craniofacial abnormalities; Epigenetics; Posttranslational modifications; Sequence analysis; Signal transduction.

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