{"doi":"10.3390/cells11071106","title":"In Vitro Characterization of Doxorubicin-Mediated Stress-Induced Premature Senescence in Human Chondrocytes","abstract":"<jats:p>Accumulation of senescent chondrocytes is thought to drive inflammatory processes and subsequent cartilage degeneration in age-related as well as posttraumatic osteoarthritis (OA). However, the underlying mechanisms of senescence and consequences on cartilage homeostasis are not completely understood so far. Therefore, suitable in vitro models are needed to study chondrocyte senescence. In this study, we established and evaluated a doxorubicin (Doxo)-based model of stress-induced premature senescence (SIPS) in human articular chondrocytes (hAC). Cellular senescence was determined by the investigation of various senescence associated (SA) hallmarks including β-galactosidase activity, expression of p16, p21, and SA secretory phenotype (SASP) markers (IL-6, IL-8, MMP-13), the presence of urokinase-type plasminogen activator receptor (uPAR), and cell cycle arrest. After seven days, Doxo-treated hAC displayed a SIPS-like phenotype, characterized by excessive secretion of SASP factors, enhanced uPAR-positivity, decreased proliferation rate, and increased β-galactosidase activity. This phenotype was proven to be stable seven days after the removal of Doxo. Moreover, Doxo-treated hAC exhibited increased granularity and flattened or fibroblast-like morphology. Further analysis implies that Doxo-mediated SIPS was driven by oxidative stress as demonstrated by increased ROS levels and NO release. Overall, we provide novel insights into chondrocyte senescence and present a suitable in vitro model for further studies.</jats:p>","journal":"Cells","year":2022,"id":631761,"datarank":1.2340713491594273,"base_score":3.912023005428146,"endowment":3.912023005428146,"self_citation_contribution":0.586803450814222,"citation_network_contribution":0.6472678983452054,"self_endowment_contribution":0.586803450814222,"citer_contribution":0.6472678983452054,"corpus_percentile":null,"corpus_rank":null,"citation_count":49,"citer_count":35,"citers_with_citation_signal":26,"citers_with_endowment":26,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1637333,"name":"Jan-Moritz Ramge","orcid":null,"position":1,"is_corresponding":false},{"id":1637334,"name":"Astrid Schoppa","orcid":"0000-0003-3559-7081","position":2,"is_corresponding":false},{"id":1036920,"name":"Anita Ignatius","orcid":"0000-0002-4782-1979","position":3,"is_corresponding":false},{"id":1637335,"name":"Jana Riegger","orcid":"0000-0003-0048-5047","position":4,"is_corresponding":false},{"id":1637332,"name":"Valeria Kirsch","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"In Vitro Characterization of Doxorubicin-Mediated Stress-Induced Premature Senescence in Human Chondrocytes","abstract":"<jats:p>Accumulation of senescent chondrocytes is thought to drive inflammatory processes and subsequent cartilage degeneration in age-related as well as posttraumatic osteoarthritis (OA). However, the underlying mechanisms of senescence and consequences on cartilage homeostasis are not completely understood so far. Therefore, suitable in vitro models are needed to study chondrocyte senescence. In this study, we established and evaluated a doxorubicin (Doxo)-based model of stress-induced premature senescence (SIPS) in human articular chondrocytes (hAC). Cellular senescence was determined by the investigation of various senescence associated (SA) hallmarks including β-galactosidase activity, expression of p16, p21, and SA secretory phenotype (SASP) markers (IL-6, IL-8, MMP-13), the presence of urokinase-type plasminogen activator receptor (uPAR), and cell cycle arrest. After seven days, Doxo-treated hAC displayed a SIPS-like phenotype, characterized by excessive secretion of SASP factors, enhanced uPAR-positivity, decreased proliferation rate, and increased β-galactosidase activity. This phenotype was proven to be stable seven days after the removal of Doxo. Moreover, Doxo-treated hAC exhibited increased granularity and flattened or fibroblast-like morphology. Further analysis implies that Doxo-mediated SIPS was driven by oxidative stress as demonstrated by increased ROS levels and NO release. Overall, we provide novel insights into chondrocyte senescence and present a suitable in vitro model for further studies.</jats:p>","is_dataset_classified":null,"base_score":3.8712010109078907,"endowment":3.8712010109078907,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35406671","pmcid":"PMC8998002","openalex_id":"https://openalex.org/W4220709306","authors":[],"funders":[{"funder_name":"German Research Foundation (DFG)","grant_id":"Project-ID 251293561","title":null},{"funder_name":"University of Ulm","grant_id":"Baustein Program","title":null},{"funder_name":"European Social Fund and by the Ministry of Science, Research and Arts Baden-Württemberg","grant_id":"Margarete von Wrangell Habilitation Program","title":null}],"total_grants":3,"fwci":5.8289,"citation_percentile":0.97066185,"influential_citations":0,"citation_trend":[{"year":2022,"count":1},{"year":2023,"count":9},{"year":2024,"count":13},{"year":2025,"count":15},{"year":2026,"count":9}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/2073-4409/11/7/1106/pdf?version=1648182859","host_type":"journal"},{"url":"https://www.mdpi.com/2073-4409/11/7/1106/pdf?version=1648182859","host_type":"publisher"},{"url":"https://www.mdpi.com/2073-4409/11/7/1106/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/cells11071106","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35406671","host_type":"repository"},{"url":"https://doaj.org/article/da324c9303e04d33aff90c5dd13555d9","host_type":"repository"},{"url":"https://dx.doi.org/10.3390/cells11071106","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8998002","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC8998002","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC8998002?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Osteoarthritis Treatment and Mechanisms","Diabetic Foot Ulcer Assessment and Management","Antimicrobial Peptides and Activities"],"mesh_terms":["beta-Galactosidase","Doxorubicin","Humans","Osteoarthritis","Cellular Senescence","Chondrocytes"],"keywords":["Senescence","Urokinase receptor","Chondrocyte","Cell biology","In vitro","Cartilage","Chemistry","Biology","Cancer research","Plasminogen activator","Endocrinology","Biochemistry","Anatomy","Aging","Chondrocytes","Oxidative stress","ROS","doxorubicin","Osteoarthritis","uPAR","SASP","Sips"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T00:37:34.894006Z","pmid":null,"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":[]}