An in vitro cell model for exploring inflammatory and amyloidogenic events in alkaptonuria.
alkaptonuria
homogentisic acid
inflammation
metabolic disease
ochronotic pigment
oxidative stress
Journal
Journal of cellular physiology
ISSN: 1097-4652
Titre abrégé: J Cell Physiol
Pays: United States
ID NLM: 0050222
Informations de publication
Date de publication:
01 Oct 2024
01 Oct 2024
Historique:
revised:
04
09
2024
received:
27
06
2024
accepted:
19
09
2024
medline:
1
10
2024
pubmed:
1
10
2024
entrez:
1
10
2024
Statut:
aheadofprint
Résumé
Alkaptonuria (AKU) is a progressive systemic inherited metabolic disorder primarily affecting the osteoarticular system, characterized by the degeneration of cartilage induced by ochronosis, ultimately leading to early osteoarthritis (OA). 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-treated 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-induced inflammatory responses, evidenced by increased production of nitric oxide, overexpression of inducible nitric oxide synthase, and cyclooxygenase-2. 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-treated cells. Overall, the C20/A4 cell model provided valuable insights into AKU pathogenesis, emphasizing its potential for facilitating drug development and therapeutic interventions.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e31449Informations de copyright
© 2024 The Author(s). Journal of Cellular Physiology published by Wiley Periodicals LLC.
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