ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/059/SRR33912759/SRR33912759_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/055/SRR33912755/SRR33912755_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/051/SRR33912751/SRR33912751_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/045/SRR33912745/SRR33912745_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/053/SRR33912753/SRR33912753_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/058/SRR33912758/SRR33912758_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/050/SRR33912750/SRR33912750_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/049/SRR33912749/SRR33912749_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/047/SRR33912747/SRR33912747_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/046/SRR33912746/SRR33912746_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/058/SRR33912758/SRR33912758_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/046/SRR33912746/SRR33912746_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/057/SRR33912757/SRR33912757_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/054/SRR33912754/SRR33912754_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/048/SRR33912748/SRR33912748_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/052/SRR33912752/SRR33912752_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/051/SRR33912751/SRR33912751_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/060/SRR33912760/SRR33912760_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/049/SRR33912749/SRR33912749_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/045/SRR33912745/SRR33912745_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/057/SRR33912757/SRR33912757_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/055/SRR33912755/SRR33912755_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/052/SRR33912752/SRR33912752_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/053/SRR33912753/SRR33912753_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/056/SRR33912756/SRR33912756_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/048/SRR33912748/SRR33912748_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/060/SRR33912760/SRR33912760_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/054/SRR33912754/SRR33912754_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/056/SRR33912756/SRR33912756_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/059/SRR33912759/SRR33912759_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/050/SRR33912750/SRR33912750_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR339/047/SRR33912747/SRR33912747_1.fastq.gzprimaryOK200GenomicsSeoul National Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA1274405Oryctolagus cuniculusThis study clarified how implant surfaces influence early osseointegration by coupling untargeted RNA sequencing with histomorphometry. Four rabbits each received three tibial implants: turned commercially pure titanium (Ti), sandblasted/large-grit/acid-etched titanium (SLA-Ti), and turned copper (Cu). Surface morphology was characterized by scanning electron microscopy, confocal microscopy, and energy dispersive spectroscopy. After 10 days, bone-to-implant contact (BIC), bone area (BA), and peri-implant transcriptomes were analyzed. Differentially expressed genes and Gene ontology (GO) enrichment were computed. SLA-Ti showed the greatest roughness. Both Ti groups yielded significantly higher BIC and BA than Cu (p < 0.001). GO terms on SLA-Ti were enriched for immune regulation and turned Cu was dominated by mitochondrial-stress pathways. Turned Ti showed minimal enrichment. SLA-Ti simultaneously up-regulated pro-inflammatory cytokines and immunoregulatory genes plus stress-adaptive markers, suggesting a balanced inflammatory milieu conducive to bone formation. Turned Cu markedly elevated mitochondrial genes and oxidative-stress markers, while suppressing antioxidant and innate-defense genes, reflecting immune-metabolic dysregulation. Turned Ti induced only modest transcript changes, consistent with passive biocompatibility. Early osseointegration hinges on a finely tuned immune-metabolic equilibrium rather than surface roughness alone. Optimal integration demands implant surfaces that trigger controlled immunomodulation while limiting oxidative stress, guiding the design of next-generation dental implants. Overall design: Four rabbits each received three tibial implants: turned commercially pure titanium (Ti), sandblasted/large-grit/acid-etched titanium (SLA-Ti), and turned copper (Cu). Surface morphology was characterized by scanning electron microscopy, confocal microscopy, and energy dispersive spectroscopy. After 10 days, bone-to-implant contact (BIC), bone area (BA), and peri-implant transcriptomes were analyzed. Differentially expressed genes and Gene ontology (GO) enrichment were computed.ENAfalseImmune-Metabolic Regulation of Early Osseointegration: Insights from Untargeted RNA SequencingImmune-Metabolic Regulation of Early Osseointegration: Insights from Untargeted RNA Sequencing2025-09-242025-06-12PRJNA1274405GSE2994249986