PRMT7 mediated PTEN activation promotes bone formation in female mice

Although the epigenetic mechanisms underlying bone formation are recognized, their specific roles and regulatory pathways remain largely unexplored. In this study, we unveil PRMT7 as a novel epigenetic modulator of MSCs osteogenic commitment. The conditional knockout of Prmt7 in mice reveals significantly impaired osteogenesis and bone regeneration exclusively in females, affecting both long bones and craniofacial structures, with no discernible impact in males. Our findings demonstrate that PRMT7 orchestrates osteogenic differentiation through a methyltransferase-dependent manner. Mechanistically, PRMT7 modulates MSCs osteogenic differentiation through the activation of PTEN. Specifically, PRMT7 augments PTEN transcription by increasing H3R2me1 levels at the PTEN promoter. Furthermore, PRMT7 interacts with the PTEN protein, and its deficiency leads to the ubiquitination and subsequent degradation of nuclear PTEN, revealing an unprecedented pathway. Crucially, PTEN overexpression ameliorates the osteogenic deficits observed in Prmt7-deficient mice. Our research positions PRMT7 as a potential therapeutic target to enhance bone formation and offers novel molecular insights into the PRMT7-PTEN regulatory axis, underscoring its significance in bone biology and regenerative medicine. Subject Categories Developmental Biology, Musculoskeletal System, Epigenetics, Post-translational Modifications