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However, investigating AKU pathology in human chondrocytes, which is crucial for understanding the disease, encounters challenges due to limited availability and donor variability. To overcome this obstacle, an in vitro model has been established using homogentisic acid (HGA) to simulate AKU conditions. This model employed immortalized C20\/A4 human chondrocytes and serves as a dependable platform for studying AKU pathogenesis. Significantly, the model demonstrates the accumulation of ochronotic pigment in HGA\u2010treated cells, consistent with findings from previous studies. Furthermore, investigations into inflammatory processes during HGA exposure revealed notable oxidative stress, as indicated by elevated levels of reactive oxygen species and lipid peroxidation. Additionally, the model demonstrated HGA\u2010induced inflammatory responses, evidenced by increased production of nitric oxide, overexpression of inducible nitric oxide synthase, and cyclooxygenase\u20102. These findings underscore the model's utility in studying inflammation associated with AKU. Moreover, analysis of serum amyloid A and serum amyloid P proteins revealed a potential interaction, corroborating evidence of amyloid fibril formation. This hypothesis was further supported by Congo red staining, which showed fibril formation exclusively in HGA\u2010treated cells. Overall, the C20\/A4 cell model provided valuable insights into AKU pathogenesis, emphasizing its potential for facilitating drug development and therapeutic interventions.<\/jats:p>","DOI":"10.1002\/jcp.31449","type":"journal-article","created":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T10:38:53Z","timestamp":1727779133000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["An in vitro cell model for exploring inflammatory and amyloidogenic events in alkaptonuria"],"prefix":"10.1002","volume":"239","author":[{"given":"Pierfrancesco","family":"Mastroeni","sequence":"first","affiliation":[{"name":"Dipartimento di Biotecnologie, Chimica e Farmacia Universit\u00e0 di Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6910-0056","authenticated-orcid":false,"given":"Michela","family":"Geminiani","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie, Chimica e Farmacia Universit\u00e0 di Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Olmastroni","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie, Chimica e Farmacia Universit\u00e0 di Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Frusciante","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie, Chimica e Farmacia Universit\u00e0 di Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Trezza","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie, Chimica e Farmacia Universit\u00e0 di Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Visibelli","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie, Chimica e Farmacia Universit\u00e0 di Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6976-9086","authenticated-orcid":false,"given":"Annalisa","family":"Santucci","sequence":"additional","affiliation":[{"name":"Dipartimento di Biotecnologie, Chimica e Farmacia Universit\u00e0 di Siena Siena Italy"},{"name":"MetabERN, Dipartimento di Biotecnologie, Chimica e Farmacia Universit\u00e0 di Siena Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/1225578"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.5152\/eurasianjmed.2018.17397"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201100358"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-024-00498-x"},{"issue":"1","key":"e_1_2_8_6_1","first-page":"75","article-title":"Chondrocyte apoptosis induced by nitric oxide","volume":"146","author":"Blanco F. 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