{"doi":"10.1172/jci179834","title":"Osteochondroprogenitor cells and neutrophils expressing p21 and senescence markers modulate fracture repair","abstract":"Cells expressing features of senescence, including upregulation of p21 and p16, appear transiently following tissue injury, yet the properties of these cells or how they contrast with age-induced senescent cells remains unclear. Here, we used skeletal injury as a model and identified the rapid appearance following fracture of p21+ cells expressing senescence markers, mainly as osteochondroprogenitors (OCHs) and neutrophils. Targeted genetic clearance of p21+ cells suppressed senescence-associated signatures within the fracture callus and accelerated fracture healing. By contrast, p21+ cell clearance did not alter bone loss due to aging; conversely, p16+ cell clearance, known to alleviate skeletal aging, did not affect fracture healing. Following fracture, p21+ neutrophils were enriched in signaling pathways known to induce paracrine stromal senescence, while p21+ OCHs were highly enriched in senescence-associated secretory phenotype factors known to impair bone formation. Further analysis revealed an injury-specific stem cell-like OCH subset that was p21+ and highly inflammatory, with a similar inflammatory mesenchymal population (fibro-adipogenic progenitors) evident following muscle injury. Thus, intercommunicating senescent-like neutrophils and mesenchymal progenitor cells were key regulators of tissue repair in bone and potentially across tissues. Moreover, our findings established contextual roles of p21+ versus p16+ senescent/senescent-like cells that may be leveraged for therapeutic opportunities.","journal":"Journal of Clinical Investigation","year":2024,"id":421345,"datarank":0.9935872297620227,"base_score":3.4657359027997265,"endowment":3.4657359027997265,"self_citation_contribution":0.519860385419959,"citation_network_contribution":0.4737268443420637,"self_endowment_contribution":0.519860385419959,"citer_contribution":0.4737268443420637,"corpus_percentile":null,"corpus_rank":null,"citation_count":31,"citer_count":29,"citers_with_citation_signal":15,"citers_with_endowment":15,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9496,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":488558,"name":"Madison L. Doolittle","orcid":"0000-0003-0912-0095","position":1,"is_corresponding":false},{"id":264538,"name":"Jennifer L. Rowsey","orcid":"0009-0005-0677-7907","position":2,"is_corresponding":false},{"id":1024641,"name":"Mitchell N. Froemming","orcid":null,"position":3,"is_corresponding":false},{"id":706616,"name":"Robyn Laura Kosinsky","orcid":"0000-0003-2869-7762","position":4,"is_corresponding":false},{"id":244089,"name":"Stephanie J. B. Vos","orcid":null,"position":5,"is_corresponding":false},{"id":243923,"name":"Ming Ruan","orcid":null,"position":6,"is_corresponding":false},{"id":233685,"name":"Nathan K. LeBrasseur","orcid":"0000-0002-2002-0418","position":7,"is_corresponding":false},{"id":263114,"name":"Abhishek Chandra","orcid":"0000-0001-9423-9669","position":8,"is_corresponding":false},{"id":233688,"name":"Robert J. Pignolo","orcid":"0000-0002-8533-9438","position":9,"is_corresponding":false},{"id":233687,"name":"João F. Passos","orcid":"0000-0001-8765-1890","position":10,"is_corresponding":false},{"id":241934,"name":"Joshua N. Farr","orcid":"0000-0002-3179-6414","position":11,"is_corresponding":false},{"id":241933,"name":"David G. Monroe","orcid":"0000-0002-4818-0114","position":12,"is_corresponding":false},{"id":233684,"name":"Sundeep Khosla","orcid":"0000-0002-2936-4372","position":13,"is_corresponding":false},{"id":804106,"name":"Dominik Saul","orcid":"0000-0002-0673-3710","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:57:36.298171Z","pmid":"38753433","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":[]}