biostudies-literatureMereness JANEI NIH HHSUniversity of RochesterNIEHS NIH HHSNational Institutes of HealthNIAMS NIH HHS117771https://www.ebi.ac.uk/biostudies/studies/S-EPMC12815593biostudies-literatureUnknown205Bone autograft healing is a highly orchestrated process that integrates immune activation, vascular ingrowth, and osteogenic remodeling. To define the molecular and cellular programs driving early autograft integration, bulk and single-cell RNA sequencing was used to analyze graft-associated tissues over 14 days in a murine periosteal-mediated autograft model. Global transcriptomic analysis revealed rapid and dynamic remodeling, with maximal gene expression changes occurring within the first week. The first 48 h were dominated by pro-inflammatory signaling, including TNF, IL-1, TLR, and MAPK pathways, accompanied by transcriptional signatures of phagocytosis and cellular clearance. These early inflammatory programs gave way to pro-regenerative signals, including activation of HIF-1, PI3K-ABoneTemporal transcriptomic profiling of bone autograft healing reveals dynamic immune, vascular, and osteogenic programs.PMC12815593T32 ES007026R01 EY033192R01 AR064200R21 EY030817Benoit DSWMereness JABasu SBenoodt LfalseTemporal transcriptomic profiling of bone autograft healing reveals dynamic immune, vascular, and osteogenic programs.Bone autograft healing is a highly orchestrated process that integrates immune activation, vascular ingrowth, and osteogenic remodeling. To define the molecular and cellular programs driving early autograft integration, bulk and single-cell RNA sequencing was used to analyze graft-associated tissues over 14 days in a murine periosteal-mediated autograft model. Global transcriptomic analysis revealed rapid and dynamic remodeling, with maximal gene expression changes occurring within the first week. The first 48 h were dominated by pro-inflammatory signaling, including TNF, IL-1, TLR, and MAPK pathways, accompanied by transcriptional signatures of phagocytosis and cellular clearance. These early inflammatory programs gave way to pro-regenerative signals, including activation of HIF-1, PI3K-A2025-01-01T00:00:00Z2025 Dec2026-06-12T05:11:17.712Z2026-06-12T03:07:45.513ZS-EPMC128155934147839210.1016/j.bone.2025.117771