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We investigated how prolonged interleukin-1\u03b2 (IL-1\u03b2) stimulation remodels the chondrocyte proteome and whether these changes are associated with senescence-associated traits. Primary human articular chondrocytes were exposed to IL-1\u03b2 (10 ng\/mL) for up to four days. Time-resolved data-independent acquisition (DIA) proteomics was integrated with immunofluorescence, quantitative PCR, multiplex metalloproteinase profiling, BrdU incorporation, growth-curve analysis, and senescence-associated \u03b2-galactosidase assays. Sustained IL-1\u03b2 induced extensive time-dependent proteomic remodeling, with early inflammatory and extracellular matrix responses followed by alterations in cell-cycle regulation and cytoskeletal organization. Prolonged stimulation was associated with persistent downregulation of CDK4, Cyclin D1, DNA replication-associated proteins, and Rho GTPase-associated components, accompanied by actin cytoskeletal remodeling. These molecular changes were associated with impaired proliferation, increased senescence-associated \u03b2-galactosidase activity, and transient modulation of p21. Following cytokine withdrawal, BrdU incorporation showed partial recovery. Together, these findings indicate that sustained IL-1\u03b2 progressively reshapes the chondrocyte cellular state through coordinated remodeling of proliferative, cytoskeletal, and metalloprotease programs while showing some degree of proliferative plasticity under the conditions tested.<\/jats:p>","DOI":"10.3390\/cells15161431","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T01:20:03Z","timestamp":1786324803000},"page":"1431","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Proteomic Dynamics Reveal Cell-Cycle and Rho GTPase Remodeling Associated with Transient Senescence Traits in Human Chondrocytes During Sustained IL-1\u03b2 Signaling"],"prefix":"10.3390","volume":"15","author":[{"given":"Hellen Paula","family":"Valerio","sequence":"first","affiliation":[{"name":"Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7002-5180","authenticated-orcid":false,"given":"Thatiana","family":"Corr\u00eaa de Melo","sequence":"additional","affiliation":[{"name":"Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3608-5320","authenticated-orcid":false,"given":"Mariana","family":"Barbosa de Souza Rizzo","sequence":"additional","affiliation":[{"name":"Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Teixeira de Melo","sequence":"additional","affiliation":[{"name":"Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7986-923X","authenticated-orcid":false,"given":"Miryam Paola","family":"Alvarez-Flores","sequence":"additional","affiliation":[{"name":"Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7717-7013","authenticated-orcid":false,"given":"Ana Marisa","family":"Chudzinski-Tavassi","sequence":"additional","affiliation":[{"name":"Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1056\/NEJMra1004965","article-title":"The Pathogenesis of Rheumatoid Arthritis","volume":"365","author":"McInnes","year":"2011","journal-title":"N. 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