{"doi":"10.1073/pnas.1918673117","title":"FOXO1 and FOXO3 transcription factors have unique functions in meniscus development and homeostasis during aging and osteoarthritis","abstract":"The objective of this study was to examine FoxO expression and FoxO function in meniscus. In menisci from human knee joints with osteoarthritis (OA), FoxO1 and 3 expression were significantly reduced compared with normal menisci from young and old normal donors. The expression of FoxO1 and 3 was also significantly reduced in mouse menisci during aging and OA induced by surgical meniscus destabilization or mechanical overuse. Deletion of FoxO1 and combined FoxO1, 3, and 4 deletions induced abnormal postnatal meniscus development in mice and these mutant mice spontaneously displayed meniscus pathology at 6 mo. Mice with Col2Cre-mediated deletion of FoxO3 or FoxO4 had normal meniscus development but had more severe aging-related damage. In mature AcanCreERT2 mice, the deletion of FoxO1, 3, and 4 aggravated meniscus lesions in all experimental OA models. FoxO deletion suppressed autophagy and antioxidant defense genes and altered several meniscus-specific genes. Expression of these genes was modulated by adenoviral FoxO1 in cultured human meniscus cells. These results suggest that FoxO1 plays a key role in meniscus development and maturation, and both FoxO1 and 3 support homeostasis and protect against meniscus damage in response to mechanical overuse and during aging and OA.","journal":"Proceedings of the National Academy of Sciences","year":2020,"id":56144,"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":87,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9604,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":291592,"name":"Sungwook Choi","orcid":"0000-0002-2656-255X","position":1,"is_corresponding":false},{"id":291593,"name":"Tokio Matsuzaki","orcid":"0000-0003-1188-5003","position":2,"is_corresponding":false},{"id":291594,"name":"O. Alvarez-Garcia","orcid":"0000-0003-0733-0566","position":3,"is_corresponding":false},{"id":291595,"name":"Merissa Olmer","orcid":"0000-0002-2483-4216","position":4,"is_corresponding":false},{"id":291596,"name":"Shawn P. Grogan","orcid":"0000-0001-8505-9316","position":5,"is_corresponding":false},{"id":291597,"name":"Darryl D. DʼLima","orcid":"0000-0002-8707-1455","position":6,"is_corresponding":false},{"id":291598,"name":"Martin Lotz","orcid":"0000-0002-6299-8799","position":7,"is_corresponding":false},{"id":291591,"name":"Kwang Lee","orcid":"0000-0002-6125-4827","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-18T21:05:49.581291Z","pmid":"31980519","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":[]}