NOX2-Driven Oxidative Stress Promotes EndMT and Uncouples Angiogenesis-Osteogenesis at the Bone-Implant Interface in Diabetes.

ABSTRACT: Diabetes undermines implant integration, yet how the bone-implant interface (BII) can be rationally re-engineered remains unclear. Here endothelial NOX2-driven oxidative stress is identified as a mechanistic switch that triggers endothelial-to-mesenchymal transition (EndMT), depletes type-H (CD31⁺EMCN⁺) vessels, and uncouples angiogenesis from osteogenesis. In a diabetic titanium-implant model, type-H endothelium and adjacent osteoprogenitors declined early (≈40% loss at 2 weeks), and peri-implant bone volume is reduced at 8 weeks (BV/TV 40.98 ± 3.96%). Pharmacologic NOX2 inhibition or endothelial-specific Nox2 deletion restored endothelial identity, suppressed EndMT and apoptosis, rebuilt type-H networks, and improved bone formation (BV/TV 53.15 ± 4.97%), yielding hi

SUBMITTER: Wu Z 

PROVIDER: S-EPMC12822455 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature