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Bone formation and differentiation are crucial for bone remodeling and repair. Protein arginine methyltransferase (PRMT) is involved in this process regulation but the specific mechanism remains unclear. This study identified TEAD3 as a arginine methylation regulatory factor for osteogenic differentiation of periodontal ligament stem cells (PDLSCs), and the methylation at position R55 can affect the formation of its own condensates and the transcriptional activity of RUNX2. This reveals the critical regulatory role of arginine methylation in TEAD3-mediated bone formation and differentiation.
01 Research Background
Bone formation and differentiation are the core processes of bone remodeling and repair. PRMT has been proven to be involved in this process regulation, but the key substrate and specific molecular mechanism remain unclear. Further exploration is urgently needed.
02 Main Content
Focus on the molecular mechanism of PRMT regulating bone formation differentiation, identify the methylation sites and functions of TEAD3, analyze the effect of its methylation status on the formation of its own condensates, the transcriptional activity of RUNX2, and the function of the Hippo signaling, and also explore the sensitivity of TEAD3 mutants to targeted inhibitory peptides.
03 Research Design
Using PDLSCs as the research model, identify the arginine methylation sites of TEAD3, construct the R55K mutant, and analyze the effects of the mutation on the formation of TEAD3 homodimer condensates, the transcriptional activity of RUNX2, and the function of the Hippo signaling through a series of experiments. Detect the response of the mutant to specific inhibitory peptides.
04 Results
TEAD3 is a arginine methylation regulatory factor for osteogenic differentiation of PDLSCs, and R55 is its conserved methylation site; the disruption of R55 methylation can enhance the formation of TEAD3 homodimer condensates, which can spatially restrict the transcriptional activity of RUNX2, but does not affect the Hippo signaling function of TEAD3; the TEAD3-R55K mutant is more sensitive to the targeted TEA domain inhibitory peptide; arginine methylation is a key switch regulating TEAD3-mediated bone formation and differentiation commitment.
05 Extension of Thoughts
Further exploration can be conducted on the cross-interaction between TEAD3 methylation and other bone metabolic regulatory pathways, and in-depth analysis of the molecular mechanism of condensate formation and its extensive regulatory effect on bone-related transcription factors, providing theoretical basis for improving the regulatory network of bone formation and differentiation.
Original source: Authors Lei Cao, Ruohui Han, Hui Xiong. Publication date: 2026-01-20. DOI: 10.1002/advs.202518597. Journal: Advanced Science.
