{"doi":"10.1101/2025.09.15.676417","title":"A Novel Proteoglycan-4 Isoform Drives Skeletal Regeneration","abstract":"Abstract Proteoglycan 4 (PRG4) is an extracellular matrix protein best known for its lubricating role in articular cartilage. Using a murine model of tibial fracture, we performed RNA-seq across multiple post-fracture timepoints and observed high Prg4 expression during the first week of healing, coinciding with the initial inflammatory phase. Single-cell RNA-seq of the fracture callus localized Prg4 expression to a stem cell population with key roles in repair. Analysis of alternative splicing in callus RNA identified a unique Prg4 isoform lacking three coding exons (hereafter termed Prg4-S ). In vivo knockdown of Prg4-S using locally delivered siRNA produced multiple defects that culminated in impaired bone formation. Together, these findings uncover an unanticipated osteogenic role for a unique Prg4 splicing isoform and highlight its potential for translational applications.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":575206,"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":0.9587,"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":478579,"name":"Deepak Kumar Khajuria","orcid":"0000-0002-3737-8504","position":1,"is_corresponding":false},{"id":770618,"name":"Christopher C. Norbury","orcid":"0000-0001-7411-6987","position":2,"is_corresponding":false},{"id":308918,"name":"Fadia Kamal","orcid":"0000-0003-2408-4061","position":3,"is_corresponding":false},{"id":478582,"name":"Reyad A. Elbarbary","orcid":"0000-0002-1006-6877","position":4,"is_corresponding":false},{"id":1483183,"name":"Mohamed A. Tantawy","orcid":"0000-0003-4014-6074","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-19T02:57:48.486077Z","pmid":"41001003","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":[]}