{"doi":"10.7554/elife.89822","title":"Activin A marks a novel progenitor cell population during fracture healing and reveals a therapeutic strategy","abstract":"Insufficient bone fracture repair represents a major clinical and societal burden and novel strategies are needed to address it. Our data reveal that the transforming growth factor-β superfamily member Activin A became very abundant during mouse and human bone fracture healing but was minimally detectable in intact bones. Single-cell RNA-sequencing revealed that the Activin A-encoding gene Inhba was highly expressed in a unique, highly proliferative progenitor cell (PPC) population with a myofibroblast character that quickly emerged after fracture and represented the center of a developmental trajectory bifurcation producing cartilage and bone cells within callus. Systemic administration of neutralizing Activin A antibody inhibited bone healing. In contrast, a single recombinant Activin A implantation at fracture site in young and aged mice boosted: PPC numbers; phosphorylated SMAD2 signaling levels; and bone repair and mechanical properties in endochondral and intramembranous healing models. Activin A directly stimulated myofibroblastic differentiation, chondrogenesis and osteogenesis in periosteal mesenchymal progenitor culture. Our data identify a distinct population of Activin A-expressing PPCs central to fracture healing and establish Activin A as a potential new therapeutic tool.","journal":"eLife","year":2023,"id":328517,"datarank":0.6884415550934442,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"self_citation_contribution":0.47670807455219194,"citation_network_contribution":0.2117334805412522,"self_endowment_contribution":0.47670807455219194,"citer_contribution":0.2117334805412522,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":18,"citers_with_citation_signal":12,"citers_with_endowment":12,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9666,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE192630"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":990764,"name":"Jiawei Lu","orcid":"0000-0003-0026-6434","position":1,"is_corresponding":false},{"id":232243,"name":"Leilei Zhong","orcid":"0000-0003-1153-4115","position":2,"is_corresponding":false},{"id":232246,"name":"Yulong Wei","orcid":"0000-0003-3823-9984","position":3,"is_corresponding":false},{"id":248326,"name":"Tao Gui","orcid":null,"position":4,"is_corresponding":false},{"id":234386,"name":"Luqiang Wang","orcid":null,"position":5,"is_corresponding":false},{"id":232253,"name":"Jaimo Ahn","orcid":"0000-0001-8151-9987","position":6,"is_corresponding":false},{"id":284964,"name":"Joel D. Boerckel","orcid":"0000-0003-3126-3025","position":7,"is_corresponding":false},{"id":432876,"name":"Danielle Rux","orcid":"0000-0002-9952-4474","position":8,"is_corresponding":false},{"id":432872,"name":"Christina Mundy","orcid":"0000-0003-3328-5965","position":9,"is_corresponding":false},{"id":232259,"name":"Ling Qin","orcid":"0000-0002-2582-0078","position":10,"is_corresponding":false},{"id":432877,"name":"Maurizio Pacifici","orcid":"0000-0001-6854-4942","position":11,"is_corresponding":false},{"id":232244,"name":"Lutian Yao","orcid":"0000-0002-0652-2075","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T01:08:52.196069Z","pmid":"38079220","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":[]}