Chondroprotective effects of Apolipoprotein D in knee osteoarthritis mice through the PI3K/AKT/mTOR signaling pathway.
Int Immunopharmacol
; 133: 112005, 2024 May 30.
Article
em En
| MEDLINE
| ID: mdl-38626543
ABSTRACT
BACKGROUND:
Because the pathophysiology of osteoarthritis (OA) has not been fully elucidated, targeted treatments are lacking. In this study, we assessed the role and underlying mechanism apolipoprotein D (APOD) on the development of OA.METHODS:
To establish an in vitro OA model, we extracted primary chondrocytes from the cartilage of C57BL/6 mice and stimulated the chondrocytes with IL-1ß. After APOD intervention or incubation with an overexpressing plasmid, we detected inflammatory-related markers using RT-qPCR, Western blotting, and ELISA. To detect apoptosis and autophagy-related markers, we used flow cytometry, immunofluorescence, and transmission electron microscopy (TEM). Finally, we measured the level of oxidative stress. We also used RNA-seq to identify the APOD-regulated downstream signaling pathways. We used an in vivo mice OA model of the anterior cruciate ligament transection (ACLT) and administered intra-articular adenovirus overexpressing APOD. To examine cartilage damage severity, we used immunohistochemical analysis (IHC), micro-CT, scanning electron microscopy (SEM), and Safranin O-fast green staining.RESULTS:
Our results showed that APOD inhibited chondrocyte inflammation, degeneration, and apoptosis induced by IL-1ß. Additionally, APOD reversed autophagy inhibition and oxidative stress and also blocked activation of the PI3K/AKT/mTOR signaling pathway induced by IL-1ß. Finally, overexpression of the APOD gene through adenovirus was sufficient to mitigate OA progression.CONCLUSIONS:
Our findings revealed that APOD had a chondroprotective role in OA progression by the PI3K/AKT/mTOR signaling pathway.Palavras-chave
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Base de dados:
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Assunto principal:
Transdução de Sinais
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Condrócitos
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Fosfatidilinositol 3-Quinases
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Osteoartrite do Joelho
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Proteínas Proto-Oncogênicas c-akt
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Apolipoproteínas D
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Serina-Treonina Quinases TOR
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article