{"doi":"10.1016/j.bone.2025.117771","title":"Temporal transcriptomic profiling of bone autograft healing reveals dynamic immune, vascular, and osteogenic programs","abstract":"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-AKT, Wnt, and BMP pathways, coincident with angiogenesis, osteogenesis, and matrix deposition. By day 14, extracellular matrix production and remodeling predominated, marked by metalloproteinase activity and structural matrix gene enrichment. Single-cell RNA sequencing revealed that donor-derived (eGFP + ) graft cells were rare and transient, whereas host-derived immune cells were progressively replaced by myofibroblasts, endothelial cells, and neurogenic cell types, including GABAergic neurons and IGSF21 + dendritic cells, suggesting active neurovascular crosstalk during healing. Together, these data define a temporal immune-to-regenerative cascade in bone autograft repair and highlight candidate cellular and molecular targets to enhance graft performance.","journal":"Bone","year":2025,"id":587505,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9393,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":705914,"name":"Sayantani Basu","orcid":null,"position":1,"is_corresponding":false},{"id":530045,"name":"Lauren Benoodt","orcid":"0000-0002-8834-8970","position":2,"is_corresponding":false},{"id":303880,"name":"Danielle S. W. Benoit","orcid":"0000-0001-7137-8164","position":3,"is_corresponding":false},{"id":565670,"name":"Jared A. Mereness","orcid":"0000-0001-9621-5580","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":null,"created_at":"2026-07-19T02:59:39.958043Z","pmid":"41478392","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}