Utx-Mediated H3k27me3 Remodeling By Nanotopography Inhibits Macrophages Inflammatory Responses

Peri-implantitis is the primary cause of dental implant failure. Nanotopography on implant surfaces enable sustained and direct regulation of immune homeostasis at the tissue interface, representing a promising strategy for preventing peri-implantitis. This study aims to investigate the mechanotransduction mechanisms underlying cellular sensing and responses to nanotopography. We fabricated titanium dioxide nanotube arrays (TNTs) through anodization, with polished pure titanium serving as a control. The impact of nanotopography on peri-implantitis was assessed in a rat model using immunohistochemistry. To explore the role of H3K27me3 in inflammation regulation, we employed immunofluorescence and Western blotting. To identify the downstream molecular mechanisms of H3K27me3, we utilized CUT&Tag and RNA-seq to reveal ATP-binding cassette transporter A1 (Abca1) as a target gene. Expression levels of Abca1 were further confirmed by qPCR and Western blotting, and its biological function was validated through siRNA-mediated knockdown. TNTs significantly attenuated the release of peri-implant inflammatory cytokines and promoted osseointegration, effects associated with reduced H3K27me3 levels. Mechanistically, the TNT surface decreased the expression of phosphorylated myosin light chain (pMLC), thereby promoting nuclear retention of the histone demethylase UTX. Consequently, enrichment of the transcriptional repression marker H3K27me3 at the Abca1 locus was reduced, leading to enhanced Abca1 expression and suppression of inflammatory responses. It was confirmed that TNTs upregulate H3K27me3-mediated Abca1 gene expression, thereby inhibiting peri-implantitis. This finding provides a novel molecular target for mechano-immunomodulatory strategies.