Inhibition of complement C3 prevents osteoarthritis progression in guinea pigs by blocking STAT1 activation.
Commun Biol
; 7(1): 370, 2024 Mar 27.
Article
em En
| MEDLINE
| ID: mdl-38538870
ABSTRACT
Osteoarthritis (OA) is one of the leading causes of disability, affecting over 500 million adults worldwide. Previous studies have found that various inflammatory factors can contribute to the pathogenesis of OA, including complement factors in the synovial fluid of OA patients. However, the pathogenesis of this disease is still not known, and the only therapy of severe OA is total joint replacements. Total joint replacements are invasive, expensive, and affect quality of life. Here we show that when human articular chondrocytes are stimulated with pro-inflammatory mediator interleukin-1ß (IL-1ß) there is an increase in inflammatory factors including complement component 3 (C3). We also found the transcription factor, signal transducer and activator of transcription 1 (STAT1), is responsible for increased C3 expression after IL-1ß stimulation in human articular chondrocytes. A specific STAT1 inhibitor, fludarabine, attenuates the hyper-expression of C3 and delays/prevents spontaneous OA in Dunkin-Hartley guinea pigs. Since fludarabine is already clinically used for chemotherapy, this study has great translational potential as a unique disease-modifying osteoarthritis drug (DMOAD) in treating primary OA.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osteoartrite
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Complemento C3
Limite:
Adult
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Animals
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article